In the published literature, this variant has been reported in individuals and families affected with breast or ovarian cancer (PMID: 29785135 (2018), 28263838 (2017), 26911350 (2016), 22486713 (2012), 16267036 (2005)). It has also been reported in unaffected individuals (PMID: 32817299 (2020), 32467295 (2020)). Additionally, a functional study suggests that the variant is not damaging to BRCA1 protein expression or function (PMID: 23867111 (2013)). The frequency of this variant in the general population, 0.000012 (3/250252 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3327_3329del (p.Lys1110del)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(14)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(8); Likely benign(4)
Uncertain significance(8); Likely benign(4)
14
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.3327_3329del (p.Lys1110del)
Variation ID: 125625 Accession: VCV000125625.34
- Type and length
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Deletion, 3 bp
- Location
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Cytogenetic: 17q21.31 17: 43092202-43092204 (GRCh38) [ NCBI UCSC ] 17: 41244219-41244221 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2014 May 1, 2024 Apr 8, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3327_3329del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Lys1110del inframe deletion NM_007294.4:c.3327_3329delAAA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001407571.1:c.3114_3116del NP_001394500.1:p.Lys1039del inframe deletion NM_001407581.1:c.3327_3329del NP_001394510.1:p.Lys1110del inframe deletion NM_001407582.1:c.3327_3329del NP_001394511.1:p.Lys1110del inframe deletion NM_001407583.1:c.3327_3329del NP_001394512.1:p.Lys1110del inframe deletion NM_001407585.1:c.3327_3329del NP_001394514.1:p.Lys1110del inframe deletion NM_001407587.1:c.3324_3326del NP_001394516.1:p.Lys1109del inframe deletion NM_001407590.1:c.3324_3326del NP_001394519.1:p.Lys1109del inframe deletion NM_001407591.1:c.3324_3326del NP_001394520.1:p.Lys1109del inframe deletion NM_001407593.1:c.3327_3329del NP_001394522.1:p.Lys1110del inframe deletion NM_001407594.1:c.3327_3329del NP_001394523.1:p.Lys1110del inframe deletion NM_001407596.1:c.3327_3329del NP_001394525.1:p.Lys1110del inframe deletion NM_001407597.1:c.3327_3329del NP_001394526.1:p.Lys1110del inframe deletion NM_001407598.1:c.3327_3329del NP_001394527.1:p.Lys1110del inframe deletion NM_001407602.1:c.3327_3329del NP_001394531.1:p.Lys1110del inframe deletion NM_001407603.1:c.3327_3329del NP_001394532.1:p.Lys1110del inframe deletion NM_001407605.1:c.3327_3329del NP_001394534.1:p.Lys1110del inframe deletion NM_001407610.1:c.3324_3326del NP_001394539.1:p.Lys1109del inframe deletion NM_001407611.1:c.3324_3326del NP_001394540.1:p.Lys1109del inframe deletion NM_001407612.1:c.3324_3326del NP_001394541.1:p.Lys1109del inframe deletion NM_001407613.1:c.3324_3326del NP_001394542.1:p.Lys1109del inframe deletion NM_001407614.1:c.3324_3326del NP_001394543.1:p.Lys1109del inframe deletion NM_001407615.1:c.3324_3326del NP_001394544.1:p.Lys1109del inframe deletion NM_001407616.1:c.3327_3329del NP_001394545.1:p.Lys1110del inframe deletion NM_001407617.1:c.3327_3329del NP_001394546.1:p.Lys1110del inframe deletion NM_001407618.1:c.3327_3329del NP_001394547.1:p.Lys1110del inframe deletion NM_001407619.1:c.3327_3329del NP_001394548.1:p.Lys1110del inframe deletion NM_001407620.1:c.3327_3329del NP_001394549.1:p.Lys1110del inframe deletion NM_001407621.1:c.3327_3329del NP_001394550.1:p.Lys1110del inframe deletion NM_001407622.1:c.3327_3329del NP_001394551.1:p.Lys1110del inframe deletion NM_001407623.1:c.3327_3329del NP_001394552.1:p.Lys1110del inframe deletion NM_001407624.1:c.3327_3329del NP_001394553.1:p.Lys1110del inframe deletion NM_001407625.1:c.3327_3329del NP_001394554.1:p.Lys1110del inframe deletion NM_001407626.1:c.3327_3329del NP_001394555.1:p.Lys1110del inframe deletion NM_001407627.1:c.3324_3326del NP_001394556.1:p.Lys1109del inframe deletion NM_001407628.1:c.3324_3326del NP_001394557.1:p.Lys1109del inframe deletion NM_001407629.1:c.3324_3326del NP_001394558.1:p.Lys1109del inframe deletion NM_001407630.1:c.3324_3326del NP_001394559.1:p.Lys1109del inframe deletion NM_001407631.1:c.3324_3326del NP_001394560.1:p.Lys1109del inframe deletion NM_001407632.1:c.3324_3326del NP_001394561.1:p.Lys1109del inframe deletion NM_001407633.1:c.3324_3326del NP_001394562.1:p.Lys1109del inframe deletion NM_001407634.1:c.3324_3326del NP_001394563.1:p.Lys1109del inframe deletion NM_001407635.1:c.3324_3326del NP_001394564.1:p.Lys1109del inframe deletion NM_001407636.1:c.3324_3326del NP_001394565.1:p.Lys1109del inframe deletion NM_001407637.1:c.3324_3326del NP_001394566.1:p.Lys1109del inframe deletion NM_001407638.1:c.3324_3326del NP_001394567.1:p.Lys1109del inframe deletion NM_001407639.1:c.3327_3329del NP_001394568.1:p.Lys1110del inframe deletion NM_001407640.1:c.3327_3329del NP_001394569.1:p.Lys1110del inframe deletion NM_001407641.1:c.3327_3329del NP_001394570.1:p.Lys1110del inframe deletion NM_001407642.1:c.3327_3329del NP_001394571.1:p.Lys1110del inframe deletion NM_001407644.1:c.3324_3326del NP_001394573.1:p.Lys1109del inframe deletion NM_001407645.1:c.3324_3326del NP_001394574.1:p.Lys1109del inframe deletion NM_001407646.1:c.3318_3320del NP_001394575.1:p.Lys1107del inframe deletion NM_001407647.1:c.3318_3320del NP_001394576.1:p.Lys1107del inframe deletion NM_001407648.1:c.3204_3206del NP_001394577.1:p.Lys1069del inframe deletion NM_001407649.1:c.3201_3203del NP_001394578.1:p.Lys1068del inframe deletion NM_001407652.1:c.3327_3329del NP_001394581.1:p.Lys1110del inframe deletion NM_001407653.1:c.3249_3251del NP_001394582.1:p.Lys1084del inframe deletion NM_001407654.1:c.3249_3251del NP_001394583.1:p.Lys1084del inframe deletion NM_001407655.1:c.3249_3251del NP_001394584.1:p.Lys1084del inframe deletion NM_001407656.1:c.3249_3251del NP_001394585.1:p.Lys1084del inframe deletion NM_001407657.1:c.3249_3251del NP_001394586.1:p.Lys1084del inframe deletion NM_001407658.1:c.3249_3251del NP_001394587.1:p.Lys1084del inframe deletion NM_001407659.1:c.3246_3248del NP_001394588.1:p.Lys1083del inframe deletion NM_001407660.1:c.3246_3248del NP_001394589.1:p.Lys1083del inframe deletion NM_001407661.1:c.3246_3248del NP_001394590.1:p.Lys1083del inframe deletion NM_001407662.1:c.3246_3248del NP_001394591.1:p.Lys1083del inframe deletion NM_001407663.1:c.3249_3251del NP_001394592.1:p.Lys1084del inframe deletion NM_001407664.1:c.3204_3206del NP_001394593.1:p.Lys1069del inframe deletion NM_001407665.1:c.3204_3206del NP_001394594.1:p.Lys1069del inframe deletion NM_001407666.1:c.3204_3206del NP_001394595.1:p.Lys1069del inframe deletion NM_001407667.1:c.3204_3206del NP_001394596.1:p.Lys1069del inframe deletion NM_001407668.1:c.3204_3206del NP_001394597.1:p.Lys1069del inframe deletion NM_001407669.1:c.3204_3206del NP_001394598.1:p.Lys1069del inframe deletion NM_001407670.1:c.3201_3203del NP_001394599.1:p.Lys1068del inframe deletion NM_001407671.1:c.3201_3203del NP_001394600.1:p.Lys1068del inframe deletion NM_001407672.1:c.3201_3203del NP_001394601.1:p.Lys1068del inframe deletion NM_001407673.1:c.3201_3203del NP_001394602.1:p.Lys1068del inframe deletion NM_001407674.1:c.3204_3206del NP_001394603.1:p.Lys1069del inframe deletion NM_001407675.1:c.3204_3206del NP_001394604.1:p.Lys1069del inframe deletion NM_001407676.1:c.3204_3206del NP_001394605.1:p.Lys1069del inframe deletion NM_001407677.1:c.3204_3206del NP_001394606.1:p.Lys1069del inframe deletion NM_001407678.1:c.3204_3206del NP_001394607.1:p.Lys1069del inframe deletion NM_001407679.1:c.3204_3206del NP_001394608.1:p.Lys1069del inframe deletion NM_001407680.1:c.3204_3206del NP_001394609.1:p.Lys1069del inframe deletion NM_001407681.1:c.3204_3206del NP_001394610.1:p.Lys1069del inframe deletion NM_001407682.1:c.3204_3206del NP_001394611.1:p.Lys1069del inframe deletion NM_001407683.1:c.3204_3206del NP_001394612.1:p.Lys1069del inframe deletion NM_001407684.1:c.3327_3329del NP_001394613.1:p.Lys1110del inframe deletion NM_001407685.1:c.3201_3203del NP_001394614.1:p.Lys1068del inframe deletion NM_001407686.1:c.3201_3203del NP_001394615.1:p.Lys1068del inframe deletion NM_001407687.1:c.3201_3203del NP_001394616.1:p.Lys1068del inframe deletion NM_001407688.1:c.3201_3203del NP_001394617.1:p.Lys1068del inframe deletion NM_001407689.1:c.3201_3203del NP_001394618.1:p.Lys1068del inframe deletion NM_001407690.1:c.3201_3203del NP_001394619.1:p.Lys1068del inframe deletion NM_001407691.1:c.3201_3203del NP_001394620.1:p.Lys1068del inframe deletion NM_001407692.1:c.3186_3188del NP_001394621.1:p.Lys1063del inframe deletion NM_001407694.1:c.3186_3188del NP_001394623.1:p.Lys1063del inframe deletion NM_001407695.1:c.3186_3188del NP_001394624.1:p.Lys1063del inframe deletion NM_001407696.1:c.3186_3188del NP_001394625.1:p.Lys1063del inframe deletion NM_001407697.1:c.3186_3188del NP_001394626.1:p.Lys1063del inframe deletion NM_001407698.1:c.3186_3188del NP_001394627.1:p.Lys1063del inframe deletion NM_001407724.1:c.3186_3188del NP_001394653.1:p.Lys1063del inframe deletion NM_001407725.1:c.3186_3188del NP_001394654.1:p.Lys1063del inframe deletion NM_001407726.1:c.3186_3188del NP_001394655.1:p.Lys1063del inframe deletion NM_001407727.1:c.3186_3188del NP_001394656.1:p.Lys1063del inframe deletion NM_001407728.1:c.3186_3188del NP_001394657.1:p.Lys1063del inframe deletion NM_001407729.1:c.3186_3188del NP_001394658.1:p.Lys1063del inframe deletion NM_001407730.1:c.3186_3188del NP_001394659.1:p.Lys1063del inframe deletion NM_001407731.1:c.3186_3188del NP_001394660.1:p.Lys1063del inframe deletion NM_001407732.1:c.3186_3188del NP_001394661.1:p.Lys1063del inframe deletion NM_001407733.1:c.3186_3188del NP_001394662.1:p.Lys1063del inframe deletion NM_001407734.1:c.3186_3188del NP_001394663.1:p.Lys1063del inframe deletion NM_001407735.1:c.3186_3188del NP_001394664.1:p.Lys1063del inframe deletion NM_001407736.1:c.3186_3188del NP_001394665.1:p.Lys1063del inframe deletion NM_001407737.1:c.3186_3188del NP_001394666.1:p.Lys1063del inframe deletion NM_001407738.1:c.3186_3188del NP_001394667.1:p.Lys1063del inframe deletion NM_001407739.1:c.3186_3188del NP_001394668.1:p.Lys1063del inframe deletion NM_001407740.1:c.3183_3185del NP_001394669.1:p.Lys1062del inframe deletion NM_001407741.1:c.3183_3185del NP_001394670.1:p.Lys1062del inframe deletion NM_001407742.1:c.3183_3185del NP_001394671.1:p.Lys1062del inframe deletion NM_001407743.1:c.3183_3185del NP_001394672.1:p.Lys1062del inframe deletion NM_001407744.1:c.3183_3185del NP_001394673.1:p.Lys1062del inframe deletion NM_001407745.1:c.3183_3185del NP_001394674.1:p.Lys1062del inframe deletion NM_001407746.1:c.3183_3185del NP_001394675.1:p.Lys1062del inframe deletion NM_001407747.1:c.3183_3185del NP_001394676.1:p.Lys1062del inframe deletion NM_001407748.1:c.3183_3185del NP_001394677.1:p.Lys1062del inframe deletion NM_001407749.1:c.3183_3185del NP_001394678.1:p.Lys1062del inframe deletion NM_001407750.1:c.3186_3188del NP_001394679.1:p.Lys1063del inframe deletion NM_001407751.1:c.3186_3188del NP_001394680.1:p.Lys1063del inframe deletion NM_001407752.1:c.3186_3188del NP_001394681.1:p.Lys1063del inframe deletion NM_001407838.1:c.3183_3185del NP_001394767.1:p.Lys1062del inframe deletion NM_001407839.1:c.3183_3185del NP_001394768.1:p.Lys1062del inframe deletion NM_001407841.1:c.3183_3185del NP_001394770.1:p.Lys1062del inframe deletion NM_001407842.1:c.3183_3185del NP_001394771.1:p.Lys1062del inframe deletion NM_001407843.1:c.3183_3185del NP_001394772.1:p.Lys1062del inframe deletion NM_001407844.1:c.3183_3185del NP_001394773.1:p.Lys1062del inframe deletion NM_001407845.1:c.3183_3185del NP_001394774.1:p.Lys1062del inframe deletion NM_001407846.1:c.3183_3185del NP_001394775.1:p.Lys1062del inframe deletion NM_001407847.1:c.3183_3185del NP_001394776.1:p.Lys1062del inframe deletion NM_001407848.1:c.3183_3185del NP_001394777.1:p.Lys1062del inframe deletion NM_001407849.1:c.3183_3185del NP_001394778.1:p.Lys1062del inframe deletion NM_001407850.1:c.3186_3188del NP_001394779.1:p.Lys1063del inframe deletion NM_001407851.1:c.3186_3188del NP_001394780.1:p.Lys1063del inframe deletion NM_001407852.1:c.3186_3188del NP_001394781.1:p.Lys1063del inframe deletion NM_001407853.1:c.3114_3116del NP_001394782.1:p.Lys1039del inframe deletion NM_001407854.1:c.3327_3329del NP_001394783.1:p.Lys1110del inframe deletion NM_001407858.1:c.3327_3329del NP_001394787.1:p.Lys1110del inframe deletion NM_001407859.1:c.3327_3329del NP_001394788.1:p.Lys1110del inframe deletion NM_001407860.1:c.3324_3326del NP_001394789.1:p.Lys1109del inframe deletion NM_001407861.1:c.3324_3326del NP_001394790.1:p.Lys1109del inframe deletion NM_001407862.1:c.3126_3128del NP_001394791.1:p.Lys1043del inframe deletion NM_001407863.1:c.3204_3206del NP_001394792.1:p.Lys1069del inframe deletion NM_001407874.1:c.3123_3125del NP_001394803.1:p.Lys1042del inframe deletion NM_001407875.1:c.3123_3125del NP_001394804.1:p.Lys1042del inframe deletion NM_001407879.1:c.3117_3119del NP_001394808.1:p.Lys1040del inframe deletion NM_001407881.1:c.3117_3119del NP_001394810.1:p.Lys1040del inframe deletion NM_001407882.1:c.3117_3119del NP_001394811.1:p.Lys1040del inframe deletion NM_001407884.1:c.3117_3119del NP_001394813.1:p.Lys1040del inframe deletion NM_001407885.1:c.3117_3119del NP_001394814.1:p.Lys1040del inframe deletion NM_001407886.1:c.3117_3119del NP_001394815.1:p.Lys1040del inframe deletion NM_001407887.1:c.3117_3119del NP_001394816.1:p.Lys1040del inframe deletion NM_001407889.1:c.3117_3119del NP_001394818.1:p.Lys1040del inframe deletion NM_001407894.1:c.3114_3116del NP_001394823.1:p.Lys1039del inframe deletion NM_001407895.1:c.3114_3116del NP_001394824.1:p.Lys1039del inframe deletion NM_001407896.1:c.3114_3116del NP_001394825.1:p.Lys1039del inframe deletion NM_001407897.1:c.3114_3116del NP_001394826.1:p.Lys1039del inframe deletion NM_001407898.1:c.3114_3116del NP_001394827.1:p.Lys1039del inframe deletion NM_001407899.1:c.3114_3116del NP_001394828.1:p.Lys1039del inframe deletion NM_001407900.1:c.3117_3119del NP_001394829.1:p.Lys1040del inframe deletion NM_001407902.1:c.3117_3119del NP_001394831.1:p.Lys1040del inframe deletion NM_001407904.1:c.3117_3119del NP_001394833.1:p.Lys1040del inframe deletion NM_001407906.1:c.3117_3119del NP_001394835.1:p.Lys1040del inframe deletion NM_001407907.1:c.3117_3119del NP_001394836.1:p.Lys1040del inframe deletion NM_001407908.1:c.3117_3119del NP_001394837.1:p.Lys1040del inframe deletion NM_001407909.1:c.3117_3119del NP_001394838.1:p.Lys1040del inframe deletion NM_001407910.1:c.3117_3119del NP_001394839.1:p.Lys1040del inframe deletion NM_001407915.1:c.3114_3116del NP_001394844.1:p.Lys1039del inframe deletion NM_001407916.1:c.3114_3116del NP_001394845.1:p.Lys1039del inframe deletion NM_001407917.1:c.3114_3116del NP_001394846.1:p.Lys1039del inframe deletion NM_001407918.1:c.3114_3116del NP_001394847.1:p.Lys1039del inframe deletion NM_001407919.1:c.3204_3206del NP_001394848.1:p.Lys1069del inframe deletion NM_001407920.1:c.3063_3065del NP_001394849.1:p.Lys1022del inframe deletion NM_001407921.1:c.3063_3065del NP_001394850.1:p.Lys1022del inframe deletion NM_001407922.1:c.3063_3065del NP_001394851.1:p.Lys1022del inframe deletion NM_001407923.1:c.3063_3065del NP_001394852.1:p.Lys1022del inframe deletion NM_001407924.1:c.3063_3065del NP_001394853.1:p.Lys1022del inframe deletion NM_001407925.1:c.3063_3065del NP_001394854.1:p.Lys1022del inframe deletion NM_001407926.1:c.3063_3065del NP_001394855.1:p.Lys1022del inframe deletion NM_001407927.1:c.3063_3065del NP_001394856.1:p.Lys1022del inframe deletion NM_001407928.1:c.3063_3065del NP_001394857.1:p.Lys1022del inframe deletion NM_001407929.1:c.3063_3065del NP_001394858.1:p.Lys1022del inframe deletion NM_001407930.1:c.3060_3062del NP_001394859.1:p.Lys1021del inframe deletion NM_001407931.1:c.3060_3062del NP_001394860.1:p.Lys1021del inframe deletion NM_001407932.1:c.3060_3062del NP_001394861.1:p.Lys1021del inframe deletion NM_001407933.1:c.3063_3065del NP_001394862.1:p.Lys1022del inframe deletion NM_001407934.1:c.3060_3062del NP_001394863.1:p.Lys1021del inframe deletion NM_001407935.1:c.3063_3065del NP_001394864.1:p.Lys1022del inframe deletion NM_001407936.1:c.3060_3062del NP_001394865.1:p.Lys1021del inframe deletion NM_001407937.1:c.3204_3206del NP_001394866.1:p.Lys1069del inframe deletion NM_001407938.1:c.3204_3206del NP_001394867.1:p.Lys1069del inframe deletion NM_001407939.1:c.3204_3206del NP_001394868.1:p.Lys1069del inframe deletion NM_001407940.1:c.3201_3203del NP_001394869.1:p.Lys1068del inframe deletion NM_001407941.1:c.3201_3203del NP_001394870.1:p.Lys1068del inframe deletion NM_001407942.1:c.3186_3188del NP_001394871.1:p.Lys1063del inframe deletion NM_001407943.1:c.3183_3185del NP_001394872.1:p.Lys1062del inframe deletion NM_001407944.1:c.3186_3188del NP_001394873.1:p.Lys1063del inframe deletion NM_001407945.1:c.3186_3188del NP_001394874.1:p.Lys1063del inframe deletion NM_001407946.1:c.2994_2996del NP_001394875.1:p.Lys999del inframe deletion NM_001407947.1:c.2994_2996del NP_001394876.1:p.Lys999del inframe deletion NM_001407948.1:c.2994_2996del NP_001394877.1:p.Lys999del inframe deletion NM_001407949.1:c.2994_2996del NP_001394878.1:p.Lys999del inframe deletion NM_001407950.1:c.2994_2996del NP_001394879.1:p.Lys999del inframe deletion NM_001407951.1:c.2994_2996del NP_001394880.1:p.Lys999del inframe deletion NM_001407952.1:c.2994_2996del NP_001394881.1:p.Lys999del inframe deletion NM_001407953.1:c.2994_2996del NP_001394882.1:p.Lys999del inframe deletion NM_001407954.1:c.2991_2993del NP_001394883.1:p.Lys998del inframe deletion NM_001407955.1:c.2991_2993del NP_001394884.1:p.Lys998del inframe deletion NM_001407956.1:c.2991_2993del NP_001394885.1:p.Lys998del inframe deletion NM_001407957.1:c.2994_2996del NP_001394886.1:p.Lys999del inframe deletion NM_001407958.1:c.2991_2993del NP_001394887.1:p.Lys998del inframe deletion NM_001407959.1:c.2946_2948del NP_001394888.1:p.Lys983del inframe deletion NM_001407960.1:c.2946_2948del NP_001394889.1:p.Lys983del inframe deletion NM_001407962.1:c.2943_2945del NP_001394891.1:p.Lys982del inframe deletion NM_001407963.1:c.2946_2948del NP_001394892.1:p.Lys983del inframe deletion NM_001407964.1:c.3183_3185del NP_001394893.1:p.Lys1062del inframe deletion NM_001407965.1:c.2823_2825del NP_001394894.1:p.Lys942del inframe deletion NM_001407966.1:c.2439_2441del NP_001394895.1:p.Lys814del inframe deletion NM_001407967.1:c.2439_2441del NP_001394896.1:p.Lys814del inframe deletion NM_001407968.1:c.788-65_788-63del intron variant NM_001407969.1:c.788-65_788-63del intron variant NM_001407970.1:c.788-1172_788-1170del intron variant NM_001407971.1:c.788-1172_788-1170del intron variant NM_001407972.1:c.785-1172_785-1170del intron variant NM_001407973.1:c.788-1172_788-1170del intron variant NM_001407974.1:c.788-1172_788-1170del intron variant NM_001407975.1:c.788-1172_788-1170del intron variant NM_001407976.1:c.788-1172_788-1170del intron variant NM_001407977.1:c.788-1172_788-1170del intron variant NM_001407978.1:c.788-1172_788-1170del intron variant NM_001407979.1:c.788-1172_788-1170del intron variant NM_001407980.1:c.788-1172_788-1170del intron variant NM_001407981.1:c.788-1172_788-1170del intron variant NM_001407982.1:c.788-1172_788-1170del intron variant NM_001407983.1:c.788-1172_788-1170del intron variant NM_001407984.1:c.785-1172_785-1170del intron variant NM_001407985.1:c.785-1172_785-1170del intron variant NM_001407986.1:c.785-1172_785-1170del intron variant NM_001407990.1:c.788-1172_788-1170del intron variant NM_001407991.1:c.785-1172_785-1170del intron variant NM_001407992.1:c.785-1172_785-1170del intron variant NM_001407993.1:c.788-1172_788-1170del intron variant NM_001408392.1:c.785-1172_785-1170del intron variant NM_001408396.1:c.785-1172_785-1170del intron variant NM_001408397.1:c.785-1172_785-1170del intron variant NM_001408398.1:c.785-1172_785-1170del intron variant NM_001408399.1:c.785-1172_785-1170del intron variant NM_001408400.1:c.785-1172_785-1170del intron variant NM_001408401.1:c.785-1172_785-1170del intron variant NM_001408402.1:c.785-1172_785-1170del intron variant NM_001408403.1:c.788-1172_788-1170del intron variant NM_001408404.1:c.788-1172_788-1170del intron variant NM_001408406.1:c.791-1181_791-1179del intron variant NM_001408407.1:c.785-1172_785-1170del intron variant NM_001408408.1:c.779-1172_779-1170del intron variant NM_001408409.1:c.710-1172_710-1170del intron variant NM_001408410.1:c.647-1172_647-1170del intron variant NM_001408411.1:c.710-1172_710-1170del intron variant NM_001408412.1:c.710-1172_710-1170del intron variant NM_001408413.1:c.707-1172_707-1170del intron variant NM_001408414.1:c.710-1172_710-1170del intron variant NM_001408415.1:c.710-1172_710-1170del intron variant NM_001408416.1:c.707-1172_707-1170del intron variant NM_001408418.1:c.671-1172_671-1170del intron variant NM_001408419.1:c.671-1172_671-1170del intron variant NM_001408420.1:c.671-1172_671-1170del intron variant NM_001408421.1:c.668-1172_668-1170del intron variant NM_001408422.1:c.671-1172_671-1170del intron variant NM_001408423.1:c.671-1172_671-1170del intron variant NM_001408424.1:c.668-1172_668-1170del intron variant NM_001408425.1:c.665-1172_665-1170del intron variant NM_001408426.1:c.665-1172_665-1170del intron variant NM_001408427.1:c.665-1172_665-1170del intron variant NM_001408428.1:c.665-1172_665-1170del intron variant NM_001408429.1:c.665-1172_665-1170del intron variant NM_001408430.1:c.665-1172_665-1170del intron variant NM_001408431.1:c.668-1172_668-1170del intron variant NM_001408432.1:c.662-1172_662-1170del intron variant NM_001408433.1:c.662-1172_662-1170del intron variant NM_001408434.1:c.662-1172_662-1170del intron variant NM_001408435.1:c.662-1172_662-1170del intron variant NM_001408436.1:c.665-1172_665-1170del intron variant NM_001408437.1:c.665-1172_665-1170del intron variant NM_001408438.1:c.665-1172_665-1170del intron variant NM_001408439.1:c.665-1172_665-1170del intron variant NM_001408440.1:c.665-1172_665-1170del intron variant NM_001408441.1:c.665-1172_665-1170del intron variant NM_001408442.1:c.665-1172_665-1170del intron variant NM_001408443.1:c.665-1172_665-1170del intron variant NM_001408444.1:c.665-1172_665-1170del intron variant NM_001408445.1:c.662-1172_662-1170del intron variant NM_001408446.1:c.662-1172_662-1170del intron variant NM_001408447.1:c.662-1172_662-1170del intron variant NM_001408448.1:c.662-1172_662-1170del intron variant NM_001408450.1:c.662-1172_662-1170del intron variant NM_001408451.1:c.653-1172_653-1170del intron variant NM_001408452.1:c.647-1172_647-1170del intron variant NM_001408453.1:c.647-1172_647-1170del intron variant NM_001408454.1:c.647-1172_647-1170del intron variant NM_001408455.1:c.647-1172_647-1170del intron variant NM_001408456.1:c.647-1172_647-1170del intron variant NM_001408457.1:c.647-1172_647-1170del intron variant NM_001408458.1:c.647-1172_647-1170del intron variant NM_001408459.1:c.647-1172_647-1170del intron variant NM_001408460.1:c.647-1172_647-1170del intron variant NM_001408461.1:c.647-1172_647-1170del intron variant NM_001408462.1:c.644-1172_644-1170del intron variant NM_001408463.1:c.644-1172_644-1170del intron variant NM_001408464.1:c.644-1172_644-1170del intron variant NM_001408465.1:c.644-1172_644-1170del intron variant NM_001408466.1:c.647-1172_647-1170del intron variant NM_001408467.1:c.647-1172_647-1170del intron variant NM_001408468.1:c.644-1172_644-1170del intron variant NM_001408469.1:c.647-1172_647-1170del intron variant NM_001408470.1:c.644-1172_644-1170del intron variant NM_001408472.1:c.788-1172_788-1170del intron variant NM_001408473.1:c.785-1172_785-1170del intron variant NM_001408474.1:c.587-1172_587-1170del intron variant NM_001408475.1:c.584-1172_584-1170del intron variant NM_001408476.1:c.587-1172_587-1170del intron variant NM_001408478.1:c.578-1172_578-1170del intron variant NM_001408479.1:c.578-1172_578-1170del intron variant NM_001408480.1:c.578-1172_578-1170del intron variant NM_001408481.1:c.578-1172_578-1170del intron variant NM_001408482.1:c.578-1172_578-1170del intron variant NM_001408483.1:c.578-1172_578-1170del intron variant NM_001408484.1:c.578-1172_578-1170del intron variant NM_001408485.1:c.578-1172_578-1170del intron variant NM_001408489.1:c.578-1172_578-1170del intron variant NM_001408490.1:c.575-1172_575-1170del intron variant NM_001408491.1:c.575-1172_575-1170del intron variant NM_001408492.1:c.578-1172_578-1170del intron variant NM_001408493.1:c.575-1172_575-1170del intron variant NM_001408494.1:c.548-1172_548-1170del intron variant NM_001408495.1:c.545-1172_545-1170del intron variant NM_001408496.1:c.524-1172_524-1170del intron variant NM_001408497.1:c.524-1172_524-1170del intron variant NM_001408498.1:c.524-1172_524-1170del intron variant NM_001408499.1:c.524-1172_524-1170del intron variant NM_001408500.1:c.524-1172_524-1170del intron variant NM_001408501.1:c.524-1172_524-1170del intron variant NM_001408502.1:c.455-1172_455-1170del intron variant NM_001408503.1:c.521-1172_521-1170del intron variant NM_001408504.1:c.521-1172_521-1170del intron variant NM_001408505.1:c.521-1172_521-1170del intron variant NM_001408506.1:c.461-1172_461-1170del intron variant NM_001408507.1:c.461-1172_461-1170del intron variant NM_001408508.1:c.452-1172_452-1170del intron variant NM_001408509.1:c.452-1172_452-1170del intron variant NM_001408510.1:c.407-1172_407-1170del intron variant NM_001408511.1:c.404-1172_404-1170del intron variant NM_001408512.1:c.284-1172_284-1170del intron variant NM_001408513.1:c.578-1172_578-1170del intron variant NM_001408514.1:c.578-1172_578-1170del intron variant NM_007294.3:c.3324_3326delAAA NP_009225.1:p.Lys1110del inframe indel NM_007294.3:c.3327_3329delAAA inframe indel NM_007297.4:c.3186_3188del NP_009228.2:p.Lys1063del inframe deletion NM_007298.4:c.788-1172_788-1170del intron variant NM_007299.4:c.788-1172_788-1170del intron variant NM_007300.4:c.3327_3329del NP_009231.2:p.Lys1110del inframe deletion NR_027676.1:n.3460_3462delAAA NC_000017.11:g.43092205_43092207del NC_000017.10:g.41244222_41244224del NG_005905.2:g.125780_125782del NG_087068.1:g.1187_1189del LRG_292:g.125780_125782del LRG_292t1:c.3327_3329del LRG_292p1:p.Lys1110del U14680.1:n.3446_3448delAAA - Protein change
- K1110del, K1063del, K1021del, K1040del, K1062del, K1107del, K982del, K999del, K1042del, K1068del, K1069del, K1084del, K814del, K1039del, K983del, K1022del, K1043del, K1083del, K942del, K998del
- Other names
-
K1109del
p.Lys1110del
- Canonical SPDI
- NC_000017.11:43092201:TTTTTT:TTT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13050 | 14856 | |
| LOC126862571 | - | - | - | GRCh38 | - | 1651 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, single submitter
|
Jan 17, 2017 | RCV000112064.10 | |
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Apr 8, 2024 | RCV000129448.22 | |
| Uncertain significance (1) |
no assertion criteria provided
|
May 21, 2018 | RCV000677819.9 | |
| Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
|
Aug 10, 2023 | RCV000590069.22 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2020 | RCV001169843.9 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV001089174.16 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 26, 2024 | RCV003226197.9 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(May 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002046737.3
First in ClinVar: Jan 01, 2022 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in individuals and families affected with breast or ovarian cancer (PMID: 29785135 (2018), 28263838 (2017), 26911350 … (more)
In the published literature, this variant has been reported in individuals and families affected with breast or ovarian cancer (PMID: 29785135 (2018), 28263838 (2017), 26911350 (2016), 22486713 (2012), 16267036 (2005)). It has also been reported in unaffected individuals (PMID: 32817299 (2020), 32467295 (2020)). Additionally, a functional study suggests that the variant is not damaging to BRCA1 protein expression or function (PMID: 23867111 (2013)). The frequency of this variant in the general population, 0.000012 (3/250252 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
|
|
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Uncertain significance
(Feb 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699017.3
First in ClinVar: Mar 17, 2018 Last updated: Apr 15, 2024 |
Comment:
Variant summary: BRCA1 c.3327_3329delAAA (p.Lys1110del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele … (more)
Variant summary: BRCA1 c.3327_3329delAAA (p.Lys1110del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 250422 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3327_3329delAAA has been reported in the literature in individuals with a personal and/or family history of breast and/or ovarian cancer without strong evidence for causality (e.g. Judkins_2005, Zanella_2017, Herzog_2021, Caputo_2021). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. A co-occurrence with a pathogenic variant (BRCA2 c.8755-1G>A) has been reported in an individual in the BIC database, providing supporting evidence for a benign role. Additionally, a publication which used a multifactorial model incorporating cosegregation data into BRCA1/2 variant classification predicted the variant to be benign (Caputo_2021). Finally, an experimental study examining a similar variant,c.3328_3330delAAG which also results in p.Lys1110del, showed that the variant was sufficient to support growth in a functional complementation assay in mouse Brca1-null embryonic stem cells and had a similar sensitivity to cisplatin as the wild-type protein, however the authors indicated that the results of these assays may not fully capture the pathogenicity of all variants in BRCA1 (Bouwman_2013) The following publications have been ascertained in the context of this evaluation (PMID: 16267036, 23867111, 19370767, 22486713, 18273839, 28263838, 34413315, 34597585). ClinVar contains an entry for this variant (Variation ID: 125625). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. (less)
|
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Likely benign
(Jul 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000184218.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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|
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Uncertain significance
(Apr 27, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Neoplasm of the breast
Affected status: yes
Allele origin:
germline
|
ACT Genomics,
Accession: SCV001250608.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant c.3327_3329delAAA (p.Lys1110del) results in a in-frame deletion of a lysine at position 1110 of the BRCA1 gene. The allele frequency of this variant … (more)
This variant c.3327_3329delAAA (p.Lys1110del) results in a in-frame deletion of a lysine at position 1110 of the BRCA1 gene. The allele frequency of this variant is 0.000054 in East Asian of gnomAD Exomes. For the insufficient evidences, this variant has been classified as variant of uncertain significance. (less)
Sex: female
Geographic origin: Taiwan
|
|
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Uncertain significance
(Feb 09, 2022)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002538198.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA1 c.3327_3329delAAA (p.K1110del) variant has been reported in heterozygosity in at least two individuals undergoing hereditary breast and ovarian cancer genetic testing (PMID: 16267036, … (more)
The BRCA1 c.3327_3329delAAA (p.K1110del) variant has been reported in heterozygosity in at least two individuals undergoing hereditary breast and ovarian cancer genetic testing (PMID: 16267036, 28263838). It has also been seen in individuals from the general population (PMID: 32467295, Flossies Database). A functional study of this variant showed that it behaved as wild-type in a cell proliferation and cisplatin sensitivity assay (PMID: 23867111). It was observed in 3/250252 chromosomes across all populations in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID 125625). The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(Jan 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV002541411.1
First in ClinVar: Jul 09, 2022 Last updated: Jul 09, 2022 |
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Likely benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000259609.9
First in ClinVar: Jan 31, 2016 Last updated: Feb 28, 2024 |
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Likely benign
(Apr 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV004814089.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
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Uncertain significance
(Jan 17, 2017)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000784882.2
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
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Likely benign
(Dec 08, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000903064.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Uncertain significance
(Nov 03, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001472409.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The BRCA1 c.3327_3329delAAA; p.Lys1110del variant (rs80357575) has been published in the literature in individuals with breast cancer (Ahmad 2012, Mehta 2018, Shah 2018). The variant … (more)
The BRCA1 c.3327_3329delAAA; p.Lys1110del variant (rs80357575) has been published in the literature in individuals with breast cancer (Ahmad 2012, Mehta 2018, Shah 2018). The variant is reported in the ClinVar database (Variation ID: 125625) and in the general population with an overall allele frequency of 0.001% (3/250,252 alleles) in the Genome Aggregation Database. The lysine at this position is moderately conserved and does not occur in a known functional domain. Additionally, at least one functional study shows this variant behaves like wild type (Bouwman 2013). Due to limited information, the clinical significance of the p.Lys1110del variant is uncertain at this time. References: Ahmad J et al. Detection of BRCA1/2 mutations in breast cancer patients from Thailand and Pakistan. Clin Genet. 2012 Dec;82(6):594-8. Bouwman P et al. A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer Discov. 2013 Oct;3(10):1142-55. Mehta A et al. Germline BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance associated with breast/ovarian cancer: a report from North India. Cancer Manag Res. 2018 Nov 30;10:6505-6516. Shah ND et al. Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients. Appl Clin Genet. 2018 May 9;11:59-67. (less)
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Uncertain significance
(Aug 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000210037.10
First in ClinVar: Feb 24, 2015 Last updated: Aug 31, 2023 |
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Observed in individuals with a personal or family history suspicious for hereditary breast and ovarian … (more)
In-frame deletion of 1 amino acid in a non-repeat region; Observed in individuals with a personal or family history suspicious for hereditary breast and ovarian cancer (Zanella et al., 2017; Caputo et al., 2021; Herzog et al., 2021; Bang et al., 2022); Functional assessment of a similar variant, c.3328_3330delAAG, also leading to the deletion of a Lysine at residue1110 demonstrated similar activity as the wild-type in a cell proliferation and cisplatin sensitivity assay (Bouwman et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as 3446_3448del; This variant is associated with the following publications: (PMID: 25036526, 16267036, 18273839, 28263838, 22486713, 31131967, 26911350, 10923033, 30555256, 29785135, 32817299, 32467295, 34597585, 34981296, 19370767, 23867111, 34413315, 36601340) (less)
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Uncertain significance
(Dec 23, 2003)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144717.1
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Uncertain significance
(May 21, 2018)
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no assertion criteria provided
Method: clinical testing
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Cancer of the pancreas
Affected status: yes
Allele origin:
germline
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3DMed Clinical Laboratory Inc
Accession: SCV000803979.1
First in ClinVar: Aug 27, 2018 Last updated: Aug 27, 2018 |
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Comment:
Comment:
Variant summary: BRCA1 c.3327_3329delAAA (p.Lys1110del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 250422 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3327_3329delAAA has been reported in the literature in individuals with a personal and/or family history of breast and/or ovarian cancer without strong evidence for causality (e.g. Judkins_2005, Zanella_2017, Herzog_2021, Caputo_2021). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. A co-occurrence with a pathogenic variant (BRCA2 c.8755-1G>A) has been reported in an individual in the BIC database, providing supporting evidence for a benign role. Additionally, a publication which used a multifactorial model incorporating cosegregation data into BRCA1/2 variant classification predicted the variant to be benign (Caputo_2021). Finally, an experimental study examining a similar variant,c.3328_3330delAAG which also results in p.Lys1110del, showed that the variant was sufficient to support growth in a functional complementation assay in mouse Brca1-null embryonic stem cells and had a similar sensitivity to cisplatin as the wild-type protein, however the authors indicated that the results of these assays may not fully capture the pathogenicity of all variants in BRCA1 (Bouwman_2013) The following publications have been ascertained in the context of this evaluation (PMID: 16267036, 23867111, 19370767, 22486713, 18273839, 28263838, 34413315, 34597585). ClinVar contains an entry for this variant (Variation ID: 125625). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant c.3327_3329delAAA (p.Lys1110del) results in a in-frame deletion of a lysine at position 1110 of the BRCA1 gene. The allele frequency of this variant is 0.000054 in East Asian of gnomAD Exomes. For the insufficient evidences, this variant has been classified as variant of uncertain significance.
Comment:
The BRCA1 c.3327_3329delAAA; p.Lys1110del variant (rs80357575) has been published in the literature in individuals with breast cancer (Ahmad 2012, Mehta 2018, Shah 2018). The variant is reported in the ClinVar database (Variation ID: 125625) and in the general population with an overall allele frequency of 0.001% (3/250,252 alleles) in the Genome Aggregation Database. The lysine at this position is moderately conserved and does not occur in a known functional domain. Additionally, at least one functional study shows this variant behaves like wild type (Bouwman 2013). Due to limited information, the clinical significance of the p.Lys1110del variant is uncertain at this time. References: Ahmad J et al. Detection of BRCA1/2 mutations in breast cancer patients from Thailand and Pakistan. Clin Genet. 2012 Dec;82(6):594-8. Bouwman P et al. A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer Discov. 2013 Oct;3(10):1142-55. Mehta A et al. Germline BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance associated with breast/ovarian cancer: a report from North India. Cancer Manag Res. 2018 Nov 30;10:6505-6516. Shah ND et al. Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients. Appl Clin Genet. 2018 May 9;11:59-67.
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Observed in individuals with a personal or family history suspicious for hereditary breast and ovarian cancer (Zanella et al., 2017; Caputo et al., 2021; Herzog et al., 2021; Bang et al., 2022); Functional assessment of a similar variant, c.3328_3330delAAG, also leading to the deletion of a Lysine at residue1110 demonstrated similar activity as the wild-type in a cell proliferation and cisplatin sensitivity assay (Bouwman et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as 3446_3448del; This variant is associated with the following publications: (PMID: 25036526, 16267036, 18273839, 28263838, 22486713, 31131967, 26911350, 10923033, 30555256, 29785135, 32817299, 32467295, 34597585, 34981296, 19370767, 23867111, 34413315, 36601340)
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
In the published literature, this variant has been reported in individuals and families affected with breast or ovarian cancer (PMID: 29785135 (2018), 28263838 (2017), 26911350 (2016), 22486713 (2012), 16267036 (2005)). It has also been reported in unaffected individuals (PMID: 32817299 (2020), 32467295 (2020)). Additionally, a functional study suggests that the variant is not damaging to BRCA1 protein expression or function (PMID: 23867111 (2013)). The frequency of this variant in the general population, 0.000012 (3/250252 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.
Comment:
Variant summary: BRCA1 c.3327_3329delAAA (p.Lys1110del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 250422 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3327_3329delAAA has been reported in the literature in individuals with a personal and/or family history of breast and/or ovarian cancer without strong evidence for causality (e.g. Judkins_2005, Zanella_2017, Herzog_2021, Caputo_2021). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. A co-occurrence with a pathogenic variant (BRCA2 c.8755-1G>A) has been reported in an individual in the BIC database, providing supporting evidence for a benign role. Additionally, a publication which used a multifactorial model incorporating cosegregation data into BRCA1/2 variant classification predicted the variant to be benign (Caputo_2021). Finally, an experimental study examining a similar variant,c.3328_3330delAAG which also results in p.Lys1110del, showed that the variant was sufficient to support growth in a functional complementation assay in mouse Brca1-null embryonic stem cells and had a similar sensitivity to cisplatin as the wild-type protein, however the authors indicated that the results of these assays may not fully capture the pathogenicity of all variants in BRCA1 (Bouwman_2013) The following publications have been ascertained in the context of this evaluation (PMID: 16267036, 23867111, 19370767, 22486713, 18273839, 28263838, 34413315, 34597585). ClinVar contains an entry for this variant (Variation ID: 125625). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant c.3327_3329delAAA (p.Lys1110del) results in a in-frame deletion of a lysine at position 1110 of the BRCA1 gene. The allele frequency of this variant is 0.000054 in East Asian of gnomAD Exomes. For the insufficient evidences, this variant has been classified as variant of uncertain significance.
Comment:
The BRCA1 c.3327_3329delAAA; p.Lys1110del variant (rs80357575) has been published in the literature in individuals with breast cancer (Ahmad 2012, Mehta 2018, Shah 2018). The variant is reported in the ClinVar database (Variation ID: 125625) and in the general population with an overall allele frequency of 0.001% (3/250,252 alleles) in the Genome Aggregation Database. The lysine at this position is moderately conserved and does not occur in a known functional domain. Additionally, at least one functional study shows this variant behaves like wild type (Bouwman 2013). Due to limited information, the clinical significance of the p.Lys1110del variant is uncertain at this time. References: Ahmad J et al. Detection of BRCA1/2 mutations in breast cancer patients from Thailand and Pakistan. Clin Genet. 2012 Dec;82(6):594-8. Bouwman P et al. A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer Discov. 2013 Oct;3(10):1142-55. Mehta A et al. Germline BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance associated with breast/ovarian cancer: a report from North India. Cancer Manag Res. 2018 Nov 30;10:6505-6516. Shah ND et al. Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients. Appl Clin Genet. 2018 May 9;11:59-67.
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Observed in individuals with a personal or family history suspicious for hereditary breast and ovarian cancer (Zanella et al., 2017; Caputo et al., 2021; Herzog et al., 2021; Bang et al., 2022); Functional assessment of a similar variant, c.3328_3330delAAG, also leading to the deletion of a Lysine at residue1110 demonstrated similar activity as the wild-type in a cell proliferation and cisplatin sensitivity assay (Bouwman et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as 3446_3448del; This variant is associated with the following publications: (PMID: 25036526, 16267036, 18273839, 28263838, 22486713, 31131967, 26911350, 10923033, 30555256, 29785135, 32817299, 32467295, 34597585, 34981296, 19370767, 23867111, 34413315, 36601340)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Profiling of the genetic features of Chinese patients with gastric cancer with HRD germline mutations in a large-scale retrospective study. | Zhang C | Journal of medical genetics | 2023 | PMID: 36627197 |
| Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach. | Caputo SM | American journal of human genetics | 2021 | PMID: 34597585 |
| Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America. | Herzog JS | NPJ breast cancer | 2021 | PMID: 34413315 |
| Can population BRCA screening be applied in non-Ashkenazi Jewish populations? Experience in Macau population. | Qin Z | Journal of medical genetics | 2021 | PMID: 32817299 |
| Prevalence of BRCA1/BRCA2 pathogenic variation in Chinese Han population. | Dong H | Journal of medical genetics | 2021 | PMID: 32467295 |
| Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
| Germline BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance associated with breast/ovarian cancer: a report from North India. | Mehta A | Cancer management and research | 2018 | PMID: 30555256 |
| Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients. | Shah ND | The application of clinical genetics | 2018 | PMID: 29785135 |
| Evaluation of the Ion Torrent PGM sequencing workflow for the routine rapid detection of BRCA1 and BRCA2 germline mutations. | Zanella I | Experimental and molecular pathology | 2017 | PMID: 28263838 |
| Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India. | Mannan AU | Journal of human genetics | 2016 | PMID: 26911350 |
| A high-throughput functional complementation assay for classification of BRCA1 missense variants. | Bouwman P | Cancer discovery | 2013 | PMID: 23867111 |
| Detection of BRCA1/2 mutations in breast cancer patients from Thailand and Pakistan. | Ahmad J | Clinical genetics | 2012 | PMID: 22486713 |
| Diagnostic guidelines for high-resolution melting curve (HRM) analysis: an interlaboratory validation of BRCA1 mutation scanning using the 96-well LightScanner. | van der Stoep N | Human mutation | 2009 | PMID: 19370767 |
| Unclassified variants identified in BRCA1 exon 11: Consequences on splicing. | Anczuków O | Genes, chromosomes & cancer | 2008 | PMID: 18273839 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
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Text-mined citations for rs80357575 ...
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the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.