In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 26306726 (2015)). A multifactorial analysis study has reported that this variant is likely not pathogenic (PMID: 31131967 (2019)). The frequency of this variant in the general population, 0.000016 (4/250354 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. 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.3362A>G (p.Asn1121Ser)
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(7); Benign(2); Likely benign(3)
Uncertain significance(7); Benign(2); Likely benign(3)
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.3362A>G (p.Asn1121Ser)
Variation ID: 37527 Accession: VCV000037527.49
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43092169 (GRCh38) [ NCBI UCSC ] 17: 41244186 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 1, 2014 May 1, 2024 Oct 27, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3362A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Asn1121Ser missense NM_001407571.1:c.3149A>G NP_001394500.1:p.Asn1050Ser missense NM_001407581.1:c.3362A>G NP_001394510.1:p.Asn1121Ser missense NM_001407582.1:c.3362A>G NP_001394511.1:p.Asn1121Ser missense NM_001407583.1:c.3362A>G NP_001394512.1:p.Asn1121Ser missense NM_001407585.1:c.3362A>G NP_001394514.1:p.Asn1121Ser missense NM_001407587.1:c.3359A>G NP_001394516.1:p.Asn1120Ser missense NM_001407590.1:c.3359A>G NP_001394519.1:p.Asn1120Ser missense NM_001407591.1:c.3359A>G NP_001394520.1:p.Asn1120Ser missense NM_001407593.1:c.3362A>G NP_001394522.1:p.Asn1121Ser missense NM_001407594.1:c.3362A>G NP_001394523.1:p.Asn1121Ser missense NM_001407596.1:c.3362A>G NP_001394525.1:p.Asn1121Ser missense NM_001407597.1:c.3362A>G NP_001394526.1:p.Asn1121Ser missense NM_001407598.1:c.3362A>G NP_001394527.1:p.Asn1121Ser missense NM_001407602.1:c.3362A>G NP_001394531.1:p.Asn1121Ser missense NM_001407603.1:c.3362A>G NP_001394532.1:p.Asn1121Ser missense NM_001407605.1:c.3362A>G NP_001394534.1:p.Asn1121Ser missense NM_001407610.1:c.3359A>G NP_001394539.1:p.Asn1120Ser missense NM_001407611.1:c.3359A>G NP_001394540.1:p.Asn1120Ser missense NM_001407612.1:c.3359A>G NP_001394541.1:p.Asn1120Ser missense NM_001407613.1:c.3359A>G NP_001394542.1:p.Asn1120Ser missense NM_001407614.1:c.3359A>G NP_001394543.1:p.Asn1120Ser missense NM_001407615.1:c.3359A>G NP_001394544.1:p.Asn1120Ser missense NM_001407616.1:c.3362A>G NP_001394545.1:p.Asn1121Ser missense NM_001407617.1:c.3362A>G NP_001394546.1:p.Asn1121Ser missense NM_001407618.1:c.3362A>G NP_001394547.1:p.Asn1121Ser missense NM_001407619.1:c.3362A>G NP_001394548.1:p.Asn1121Ser missense NM_001407620.1:c.3362A>G NP_001394549.1:p.Asn1121Ser missense NM_001407621.1:c.3362A>G NP_001394550.1:p.Asn1121Ser missense NM_001407622.1:c.3362A>G NP_001394551.1:p.Asn1121Ser missense NM_001407623.1:c.3362A>G NP_001394552.1:p.Asn1121Ser missense NM_001407624.1:c.3362A>G NP_001394553.1:p.Asn1121Ser missense NM_001407625.1:c.3362A>G NP_001394554.1:p.Asn1121Ser missense NM_001407626.1:c.3362A>G NP_001394555.1:p.Asn1121Ser missense NM_001407627.1:c.3359A>G NP_001394556.1:p.Asn1120Ser missense NM_001407628.1:c.3359A>G NP_001394557.1:p.Asn1120Ser missense NM_001407629.1:c.3359A>G NP_001394558.1:p.Asn1120Ser missense NM_001407630.1:c.3359A>G NP_001394559.1:p.Asn1120Ser missense NM_001407631.1:c.3359A>G NP_001394560.1:p.Asn1120Ser missense NM_001407632.1:c.3359A>G NP_001394561.1:p.Asn1120Ser missense NM_001407633.1:c.3359A>G NP_001394562.1:p.Asn1120Ser missense NM_001407634.1:c.3359A>G NP_001394563.1:p.Asn1120Ser missense NM_001407635.1:c.3359A>G NP_001394564.1:p.Asn1120Ser missense NM_001407636.1:c.3359A>G NP_001394565.1:p.Asn1120Ser missense NM_001407637.1:c.3359A>G NP_001394566.1:p.Asn1120Ser missense NM_001407638.1:c.3359A>G NP_001394567.1:p.Asn1120Ser missense NM_001407639.1:c.3362A>G NP_001394568.1:p.Asn1121Ser missense NM_001407640.1:c.3362A>G NP_001394569.1:p.Asn1121Ser missense NM_001407641.1:c.3362A>G NP_001394570.1:p.Asn1121Ser missense NM_001407642.1:c.3362A>G NP_001394571.1:p.Asn1121Ser missense NM_001407644.1:c.3359A>G NP_001394573.1:p.Asn1120Ser missense NM_001407645.1:c.3359A>G NP_001394574.1:p.Asn1120Ser missense NM_001407646.1:c.3353A>G NP_001394575.1:p.Asn1118Ser missense NM_001407647.1:c.3353A>G NP_001394576.1:p.Asn1118Ser missense NM_001407648.1:c.3239A>G NP_001394577.1:p.Asn1080Ser missense NM_001407649.1:c.3236A>G NP_001394578.1:p.Asn1079Ser missense NM_001407652.1:c.3362A>G NP_001394581.1:p.Asn1121Ser missense NM_001407653.1:c.3284A>G NP_001394582.1:p.Asn1095Ser missense NM_001407654.1:c.3284A>G NP_001394583.1:p.Asn1095Ser missense NM_001407655.1:c.3284A>G NP_001394584.1:p.Asn1095Ser missense NM_001407656.1:c.3284A>G NP_001394585.1:p.Asn1095Ser missense NM_001407657.1:c.3284A>G NP_001394586.1:p.Asn1095Ser missense NM_001407658.1:c.3284A>G NP_001394587.1:p.Asn1095Ser missense NM_001407659.1:c.3281A>G NP_001394588.1:p.Asn1094Ser missense NM_001407660.1:c.3281A>G NP_001394589.1:p.Asn1094Ser missense NM_001407661.1:c.3281A>G NP_001394590.1:p.Asn1094Ser missense NM_001407662.1:c.3281A>G NP_001394591.1:p.Asn1094Ser missense NM_001407663.1:c.3284A>G NP_001394592.1:p.Asn1095Ser missense NM_001407664.1:c.3239A>G NP_001394593.1:p.Asn1080Ser missense NM_001407665.1:c.3239A>G NP_001394594.1:p.Asn1080Ser missense NM_001407666.1:c.3239A>G NP_001394595.1:p.Asn1080Ser missense NM_001407667.1:c.3239A>G NP_001394596.1:p.Asn1080Ser missense NM_001407668.1:c.3239A>G NP_001394597.1:p.Asn1080Ser missense NM_001407669.1:c.3239A>G NP_001394598.1:p.Asn1080Ser missense NM_001407670.1:c.3236A>G NP_001394599.1:p.Asn1079Ser missense NM_001407671.1:c.3236A>G NP_001394600.1:p.Asn1079Ser missense NM_001407672.1:c.3236A>G NP_001394601.1:p.Asn1079Ser missense NM_001407673.1:c.3236A>G NP_001394602.1:p.Asn1079Ser missense NM_001407674.1:c.3239A>G NP_001394603.1:p.Asn1080Ser missense NM_001407675.1:c.3239A>G NP_001394604.1:p.Asn1080Ser missense NM_001407676.1:c.3239A>G NP_001394605.1:p.Asn1080Ser missense NM_001407677.1:c.3239A>G NP_001394606.1:p.Asn1080Ser missense NM_001407678.1:c.3239A>G NP_001394607.1:p.Asn1080Ser missense NM_001407679.1:c.3239A>G NP_001394608.1:p.Asn1080Ser missense NM_001407680.1:c.3239A>G NP_001394609.1:p.Asn1080Ser missense NM_001407681.1:c.3239A>G NP_001394610.1:p.Asn1080Ser missense NM_001407682.1:c.3239A>G NP_001394611.1:p.Asn1080Ser missense NM_001407683.1:c.3239A>G NP_001394612.1:p.Asn1080Ser missense NM_001407684.1:c.3362A>G NP_001394613.1:p.Asn1121Ser missense NM_001407685.1:c.3236A>G NP_001394614.1:p.Asn1079Ser missense NM_001407686.1:c.3236A>G NP_001394615.1:p.Asn1079Ser missense NM_001407687.1:c.3236A>G NP_001394616.1:p.Asn1079Ser missense NM_001407688.1:c.3236A>G NP_001394617.1:p.Asn1079Ser missense NM_001407689.1:c.3236A>G NP_001394618.1:p.Asn1079Ser missense NM_001407690.1:c.3236A>G NP_001394619.1:p.Asn1079Ser missense NM_001407691.1:c.3236A>G NP_001394620.1:p.Asn1079Ser missense NM_001407692.1:c.3221A>G NP_001394621.1:p.Asn1074Ser missense NM_001407694.1:c.3221A>G NP_001394623.1:p.Asn1074Ser missense NM_001407695.1:c.3221A>G NP_001394624.1:p.Asn1074Ser missense NM_001407696.1:c.3221A>G NP_001394625.1:p.Asn1074Ser missense NM_001407697.1:c.3221A>G NP_001394626.1:p.Asn1074Ser missense NM_001407698.1:c.3221A>G NP_001394627.1:p.Asn1074Ser missense NM_001407724.1:c.3221A>G NP_001394653.1:p.Asn1074Ser missense NM_001407725.1:c.3221A>G NP_001394654.1:p.Asn1074Ser missense NM_001407726.1:c.3221A>G NP_001394655.1:p.Asn1074Ser missense NM_001407727.1:c.3221A>G NP_001394656.1:p.Asn1074Ser missense NM_001407728.1:c.3221A>G NP_001394657.1:p.Asn1074Ser missense NM_001407729.1:c.3221A>G NP_001394658.1:p.Asn1074Ser missense NM_001407730.1:c.3221A>G NP_001394659.1:p.Asn1074Ser missense NM_001407731.1:c.3221A>G NP_001394660.1:p.Asn1074Ser missense NM_001407732.1:c.3221A>G NP_001394661.1:p.Asn1074Ser missense NM_001407733.1:c.3221A>G NP_001394662.1:p.Asn1074Ser missense NM_001407734.1:c.3221A>G NP_001394663.1:p.Asn1074Ser missense NM_001407735.1:c.3221A>G NP_001394664.1:p.Asn1074Ser missense NM_001407736.1:c.3221A>G NP_001394665.1:p.Asn1074Ser missense NM_001407737.1:c.3221A>G NP_001394666.1:p.Asn1074Ser missense NM_001407738.1:c.3221A>G NP_001394667.1:p.Asn1074Ser missense NM_001407739.1:c.3221A>G NP_001394668.1:p.Asn1074Ser missense NM_001407740.1:c.3218A>G NP_001394669.1:p.Asn1073Ser missense NM_001407741.1:c.3218A>G NP_001394670.1:p.Asn1073Ser missense NM_001407742.1:c.3218A>G NP_001394671.1:p.Asn1073Ser missense NM_001407743.1:c.3218A>G NP_001394672.1:p.Asn1073Ser missense NM_001407744.1:c.3218A>G NP_001394673.1:p.Asn1073Ser missense NM_001407745.1:c.3218A>G NP_001394674.1:p.Asn1073Ser missense NM_001407746.1:c.3218A>G NP_001394675.1:p.Asn1073Ser missense NM_001407747.1:c.3218A>G NP_001394676.1:p.Asn1073Ser missense NM_001407748.1:c.3218A>G NP_001394677.1:p.Asn1073Ser missense NM_001407749.1:c.3218A>G NP_001394678.1:p.Asn1073Ser missense NM_001407750.1:c.3221A>G NP_001394679.1:p.Asn1074Ser missense NM_001407751.1:c.3221A>G NP_001394680.1:p.Asn1074Ser missense NM_001407752.1:c.3221A>G NP_001394681.1:p.Asn1074Ser missense NM_001407838.1:c.3218A>G NP_001394767.1:p.Asn1073Ser missense NM_001407839.1:c.3218A>G NP_001394768.1:p.Asn1073Ser missense NM_001407841.1:c.3218A>G NP_001394770.1:p.Asn1073Ser missense NM_001407842.1:c.3218A>G NP_001394771.1:p.Asn1073Ser missense NM_001407843.1:c.3218A>G NP_001394772.1:p.Asn1073Ser missense NM_001407844.1:c.3218A>G NP_001394773.1:p.Asn1073Ser missense NM_001407845.1:c.3218A>G NP_001394774.1:p.Asn1073Ser missense NM_001407846.1:c.3218A>G NP_001394775.1:p.Asn1073Ser missense NM_001407847.1:c.3218A>G NP_001394776.1:p.Asn1073Ser missense NM_001407848.1:c.3218A>G NP_001394777.1:p.Asn1073Ser missense NM_001407849.1:c.3218A>G NP_001394778.1:p.Asn1073Ser missense NM_001407850.1:c.3221A>G NP_001394779.1:p.Asn1074Ser missense NM_001407851.1:c.3221A>G NP_001394780.1:p.Asn1074Ser missense NM_001407852.1:c.3221A>G NP_001394781.1:p.Asn1074Ser missense NM_001407853.1:c.3149A>G NP_001394782.1:p.Asn1050Ser missense NM_001407854.1:c.3362A>G NP_001394783.1:p.Asn1121Ser missense NM_001407858.1:c.3362A>G NP_001394787.1:p.Asn1121Ser missense NM_001407859.1:c.3362A>G NP_001394788.1:p.Asn1121Ser missense NM_001407860.1:c.3359A>G NP_001394789.1:p.Asn1120Ser missense NM_001407861.1:c.3359A>G NP_001394790.1:p.Asn1120Ser missense NM_001407862.1:c.3161A>G NP_001394791.1:p.Asn1054Ser missense NM_001407863.1:c.3239A>G NP_001394792.1:p.Asn1080Ser missense NM_001407874.1:c.3158A>G NP_001394803.1:p.Asn1053Ser missense NM_001407875.1:c.3158A>G NP_001394804.1:p.Asn1053Ser missense NM_001407879.1:c.3152A>G NP_001394808.1:p.Asn1051Ser missense NM_001407881.1:c.3152A>G NP_001394810.1:p.Asn1051Ser missense NM_001407882.1:c.3152A>G NP_001394811.1:p.Asn1051Ser missense NM_001407884.1:c.3152A>G NP_001394813.1:p.Asn1051Ser missense NM_001407885.1:c.3152A>G NP_001394814.1:p.Asn1051Ser missense NM_001407886.1:c.3152A>G NP_001394815.1:p.Asn1051Ser missense NM_001407887.1:c.3152A>G NP_001394816.1:p.Asn1051Ser missense NM_001407889.1:c.3152A>G NP_001394818.1:p.Asn1051Ser missense NM_001407894.1:c.3149A>G NP_001394823.1:p.Asn1050Ser missense NM_001407895.1:c.3149A>G NP_001394824.1:p.Asn1050Ser missense NM_001407896.1:c.3149A>G NP_001394825.1:p.Asn1050Ser missense NM_001407897.1:c.3149A>G NP_001394826.1:p.Asn1050Ser missense NM_001407898.1:c.3149A>G NP_001394827.1:p.Asn1050Ser missense NM_001407899.1:c.3149A>G NP_001394828.1:p.Asn1050Ser missense NM_001407900.1:c.3152A>G NP_001394829.1:p.Asn1051Ser missense NM_001407902.1:c.3152A>G NP_001394831.1:p.Asn1051Ser missense NM_001407904.1:c.3152A>G NP_001394833.1:p.Asn1051Ser missense NM_001407906.1:c.3152A>G NP_001394835.1:p.Asn1051Ser missense NM_001407907.1:c.3152A>G NP_001394836.1:p.Asn1051Ser missense NM_001407908.1:c.3152A>G NP_001394837.1:p.Asn1051Ser missense NM_001407909.1:c.3152A>G NP_001394838.1:p.Asn1051Ser missense NM_001407910.1:c.3152A>G NP_001394839.1:p.Asn1051Ser missense NM_001407915.1:c.3149A>G NP_001394844.1:p.Asn1050Ser missense NM_001407916.1:c.3149A>G NP_001394845.1:p.Asn1050Ser missense NM_001407917.1:c.3149A>G NP_001394846.1:p.Asn1050Ser missense NM_001407918.1:c.3149A>G NP_001394847.1:p.Asn1050Ser missense NM_001407919.1:c.3239A>G NP_001394848.1:p.Asn1080Ser missense NM_001407920.1:c.3098A>G NP_001394849.1:p.Asn1033Ser missense NM_001407921.1:c.3098A>G NP_001394850.1:p.Asn1033Ser missense NM_001407922.1:c.3098A>G NP_001394851.1:p.Asn1033Ser missense NM_001407923.1:c.3098A>G NP_001394852.1:p.Asn1033Ser missense NM_001407924.1:c.3098A>G NP_001394853.1:p.Asn1033Ser missense NM_001407925.1:c.3098A>G NP_001394854.1:p.Asn1033Ser missense NM_001407926.1:c.3098A>G NP_001394855.1:p.Asn1033Ser missense NM_001407927.1:c.3098A>G NP_001394856.1:p.Asn1033Ser missense NM_001407928.1:c.3098A>G NP_001394857.1:p.Asn1033Ser missense NM_001407929.1:c.3098A>G NP_001394858.1:p.Asn1033Ser missense NM_001407930.1:c.3095A>G NP_001394859.1:p.Asn1032Ser missense NM_001407931.1:c.3095A>G NP_001394860.1:p.Asn1032Ser missense NM_001407932.1:c.3095A>G NP_001394861.1:p.Asn1032Ser missense NM_001407933.1:c.3098A>G NP_001394862.1:p.Asn1033Ser missense NM_001407934.1:c.3095A>G NP_001394863.1:p.Asn1032Ser missense NM_001407935.1:c.3098A>G NP_001394864.1:p.Asn1033Ser missense NM_001407936.1:c.3095A>G NP_001394865.1:p.Asn1032Ser missense NM_001407937.1:c.3239A>G NP_001394866.1:p.Asn1080Ser missense NM_001407938.1:c.3239A>G NP_001394867.1:p.Asn1080Ser missense NM_001407939.1:c.3239A>G NP_001394868.1:p.Asn1080Ser missense NM_001407940.1:c.3236A>G NP_001394869.1:p.Asn1079Ser missense NM_001407941.1:c.3236A>G NP_001394870.1:p.Asn1079Ser missense NM_001407942.1:c.3221A>G NP_001394871.1:p.Asn1074Ser missense NM_001407943.1:c.3218A>G NP_001394872.1:p.Asn1073Ser missense NM_001407944.1:c.3221A>G NP_001394873.1:p.Asn1074Ser missense NM_001407945.1:c.3221A>G NP_001394874.1:p.Asn1074Ser missense NM_001407946.1:c.3029A>G NP_001394875.1:p.Asn1010Ser missense NM_001407947.1:c.3029A>G NP_001394876.1:p.Asn1010Ser missense NM_001407948.1:c.3029A>G NP_001394877.1:p.Asn1010Ser missense NM_001407949.1:c.3029A>G NP_001394878.1:p.Asn1010Ser missense NM_001407950.1:c.3029A>G NP_001394879.1:p.Asn1010Ser missense NM_001407951.1:c.3029A>G NP_001394880.1:p.Asn1010Ser missense NM_001407952.1:c.3029A>G NP_001394881.1:p.Asn1010Ser missense NM_001407953.1:c.3029A>G NP_001394882.1:p.Asn1010Ser missense NM_001407954.1:c.3026A>G NP_001394883.1:p.Asn1009Ser missense NM_001407955.1:c.3026A>G NP_001394884.1:p.Asn1009Ser missense NM_001407956.1:c.3026A>G NP_001394885.1:p.Asn1009Ser missense NM_001407957.1:c.3029A>G NP_001394886.1:p.Asn1010Ser missense NM_001407958.1:c.3026A>G NP_001394887.1:p.Asn1009Ser missense NM_001407959.1:c.2981A>G NP_001394888.1:p.Asn994Ser missense NM_001407960.1:c.2981A>G NP_001394889.1:p.Asn994Ser missense NM_001407962.1:c.2978A>G NP_001394891.1:p.Asn993Ser missense NM_001407963.1:c.2981A>G NP_001394892.1:p.Asn994Ser missense NM_001407964.1:c.3218A>G NP_001394893.1:p.Asn1073Ser missense NM_001407965.1:c.2858A>G NP_001394894.1:p.Asn953Ser missense NM_001407966.1:c.2474A>G NP_001394895.1:p.Asn825Ser missense NM_001407967.1:c.2474A>G NP_001394896.1:p.Asn825Ser missense NM_001407968.1:c.788-30A>G intron variant NM_001407969.1:c.788-30A>G intron variant NM_001407970.1:c.788-1137A>G intron variant NM_001407971.1:c.788-1137A>G intron variant NM_001407972.1:c.785-1137A>G intron variant NM_001407973.1:c.788-1137A>G intron variant NM_001407974.1:c.788-1137A>G intron variant NM_001407975.1:c.788-1137A>G intron variant NM_001407976.1:c.788-1137A>G intron variant NM_001407977.1:c.788-1137A>G intron variant NM_001407978.1:c.788-1137A>G intron variant NM_001407979.1:c.788-1137A>G intron variant NM_001407980.1:c.788-1137A>G intron variant NM_001407981.1:c.788-1137A>G intron variant NM_001407982.1:c.788-1137A>G intron variant NM_001407983.1:c.788-1137A>G intron variant NM_001407984.1:c.785-1137A>G intron variant NM_001407985.1:c.785-1137A>G intron variant NM_001407986.1:c.785-1137A>G intron variant NM_001407990.1:c.788-1137A>G intron variant NM_001407991.1:c.785-1137A>G intron variant NM_001407992.1:c.785-1137A>G intron variant NM_001407993.1:c.788-1137A>G intron variant NM_001408392.1:c.785-1137A>G intron variant NM_001408396.1:c.785-1137A>G intron variant NM_001408397.1:c.785-1137A>G intron variant NM_001408398.1:c.785-1137A>G intron variant NM_001408399.1:c.785-1137A>G intron variant NM_001408400.1:c.785-1137A>G intron variant NM_001408401.1:c.785-1137A>G intron variant NM_001408402.1:c.785-1137A>G intron variant NM_001408403.1:c.788-1137A>G intron variant NM_001408404.1:c.788-1137A>G intron variant NM_001408406.1:c.791-1146A>G intron variant NM_001408407.1:c.785-1137A>G intron variant NM_001408408.1:c.779-1137A>G intron variant NM_001408409.1:c.710-1137A>G intron variant NM_001408410.1:c.647-1137A>G intron variant NM_001408411.1:c.710-1137A>G intron variant NM_001408412.1:c.710-1137A>G intron variant NM_001408413.1:c.707-1137A>G intron variant NM_001408414.1:c.710-1137A>G intron variant NM_001408415.1:c.710-1137A>G intron variant NM_001408416.1:c.707-1137A>G intron variant NM_001408418.1:c.671-1137A>G intron variant NM_001408419.1:c.671-1137A>G intron variant NM_001408420.1:c.671-1137A>G intron variant NM_001408421.1:c.668-1137A>G intron variant NM_001408422.1:c.671-1137A>G intron variant NM_001408423.1:c.671-1137A>G intron variant NM_001408424.1:c.668-1137A>G intron variant NM_001408425.1:c.665-1137A>G intron variant NM_001408426.1:c.665-1137A>G intron variant NM_001408427.1:c.665-1137A>G intron variant NM_001408428.1:c.665-1137A>G intron variant NM_001408429.1:c.665-1137A>G intron variant NM_001408430.1:c.665-1137A>G intron variant NM_001408431.1:c.668-1137A>G intron variant NM_001408432.1:c.662-1137A>G intron variant NM_001408433.1:c.662-1137A>G intron variant NM_001408434.1:c.662-1137A>G intron variant NM_001408435.1:c.662-1137A>G intron variant NM_001408436.1:c.665-1137A>G intron variant NM_001408437.1:c.665-1137A>G intron variant NM_001408438.1:c.665-1137A>G intron variant NM_001408439.1:c.665-1137A>G intron variant NM_001408440.1:c.665-1137A>G intron variant NM_001408441.1:c.665-1137A>G intron variant NM_001408442.1:c.665-1137A>G intron variant NM_001408443.1:c.665-1137A>G intron variant NM_001408444.1:c.665-1137A>G intron variant NM_001408445.1:c.662-1137A>G intron variant NM_001408446.1:c.662-1137A>G intron variant NM_001408447.1:c.662-1137A>G intron variant NM_001408448.1:c.662-1137A>G intron variant NM_001408450.1:c.662-1137A>G intron variant NM_001408451.1:c.653-1137A>G intron variant NM_001408452.1:c.647-1137A>G intron variant NM_001408453.1:c.647-1137A>G intron variant NM_001408454.1:c.647-1137A>G intron variant NM_001408455.1:c.647-1137A>G intron variant NM_001408456.1:c.647-1137A>G intron variant NM_001408457.1:c.647-1137A>G intron variant NM_001408458.1:c.647-1137A>G intron variant NM_001408459.1:c.647-1137A>G intron variant NM_001408460.1:c.647-1137A>G intron variant NM_001408461.1:c.647-1137A>G intron variant NM_001408462.1:c.644-1137A>G intron variant NM_001408463.1:c.644-1137A>G intron variant NM_001408464.1:c.644-1137A>G intron variant NM_001408465.1:c.644-1137A>G intron variant NM_001408466.1:c.647-1137A>G intron variant NM_001408467.1:c.647-1137A>G intron variant NM_001408468.1:c.644-1137A>G intron variant NM_001408469.1:c.647-1137A>G intron variant NM_001408470.1:c.644-1137A>G intron variant NM_001408472.1:c.788-1137A>G intron variant NM_001408473.1:c.785-1137A>G intron variant NM_001408474.1:c.587-1137A>G intron variant NM_001408475.1:c.584-1137A>G intron variant NM_001408476.1:c.587-1137A>G intron variant NM_001408478.1:c.578-1137A>G intron variant NM_001408479.1:c.578-1137A>G intron variant NM_001408480.1:c.578-1137A>G intron variant NM_001408481.1:c.578-1137A>G intron variant NM_001408482.1:c.578-1137A>G intron variant NM_001408483.1:c.578-1137A>G intron variant NM_001408484.1:c.578-1137A>G intron variant NM_001408485.1:c.578-1137A>G intron variant NM_001408489.1:c.578-1137A>G intron variant NM_001408490.1:c.575-1137A>G intron variant NM_001408491.1:c.575-1137A>G intron variant NM_001408492.1:c.578-1137A>G intron variant NM_001408493.1:c.575-1137A>G intron variant NM_001408494.1:c.548-1137A>G intron variant NM_001408495.1:c.545-1137A>G intron variant NM_001408496.1:c.524-1137A>G intron variant NM_001408497.1:c.524-1137A>G intron variant NM_001408498.1:c.524-1137A>G intron variant NM_001408499.1:c.524-1137A>G intron variant NM_001408500.1:c.524-1137A>G intron variant NM_001408501.1:c.524-1137A>G intron variant NM_001408502.1:c.455-1137A>G intron variant NM_001408503.1:c.521-1137A>G intron variant NM_001408504.1:c.521-1137A>G intron variant NM_001408505.1:c.521-1137A>G intron variant NM_001408506.1:c.461-1137A>G intron variant NM_001408507.1:c.461-1137A>G intron variant NM_001408508.1:c.452-1137A>G intron variant NM_001408509.1:c.452-1137A>G intron variant NM_001408510.1:c.407-1137A>G intron variant NM_001408511.1:c.404-1137A>G intron variant NM_001408512.1:c.284-1137A>G intron variant NM_001408513.1:c.578-1137A>G intron variant NM_001408514.1:c.578-1137A>G intron variant NM_007297.4:c.3221A>G NP_009228.2:p.Asn1074Ser missense NM_007298.4:c.788-1137A>G intron variant NM_007299.4:c.788-1137A>G intron variant NM_007300.4:c.3362A>G NP_009231.2:p.Asn1121Ser missense NR_027676.1:n.3498A>G NC_000017.11:g.43092169T>C NC_000017.10:g.41244186T>C NG_005905.2:g.125815A>G NG_087068.1:g.1151T>C LRG_292:g.125815A>G LRG_292t1:c.3362A>G LRG_292p1:p.Asn1121Ser U14680.1:n.3481A>G - Protein change
- N1121S, N1074S, N1009S, N1010S, N1053S, N1095S, N825S, N1033S, N1050S, N1054S, N1080S, N1120S, N953S, N1094S, N994S, N1032S, N1051S, N1073S, N1079S, N1118S, N993S
- Other names
-
NP_009225.1:p.Asn1121Ser
3481A>G
- Canonical SPDI
- NC_000017.11:43092168:T:C
-
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.
-
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
- 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 (3) |
criteria provided, single submitter
|
Sep 26, 2016 | RCV000031108.16 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Oct 27, 2023 | RCV000048166.23 | |
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Mar 23, 2023 | RCV000569556.16 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 3, 2019 | RCV000425661.13 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
May 12, 2023 | RCV001697097.17 |
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 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600329.3
First in ClinVar: Mar 08, 2017 Last updated: Jan 06, 2024 |
Comment:
In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 26306726 (2015)). A multifactorial analysis study has reported that … (more)
In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 26306726 (2015)). A multifactorial analysis study has reported that this variant is likely not pathogenic (PMID: 31131967 (2019)). The frequency of this variant in the general population, 0.000016 (4/250354 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
|
|
|
Likely benign
(Dec 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000526285.5
First in ClinVar: Mar 08, 2017 Last updated: Sep 25, 2021 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26306726, 31131967)
|
|
|
Uncertain significance
(Nov 19, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002538202.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA1 c.3362A>G (p.N1121S) variant has been reported in heterozygosity in at least one individual with ovarian cancer (PMID: 26306726). This variant was observed in … (more)
The BRCA1 c.3362A>G (p.N1121S) variant has been reported in heterozygosity in at least one individual with ovarian cancer (PMID: 26306726). This variant was observed in 2/16058 chromosomes in the African population according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654), and has been reported in ClinVar (Variation ID: 37527). Functional studies have not been performed, and in silico predictions of the variant's effect on protein function are inconclusive. Based on the current evidence available, this variant is interpreted as a variant of uncertain significance. (less)
|
|
|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003851987.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
|
Benign
(Sep 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000903504.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
|
Uncertain significance
(Oct 03, 2019)
|
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: SCV001363930.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BRCA1 c.3362A>G (p.Asn1121Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: BRCA1 c.3362A>G (p.Asn1121Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250354 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3362A>G has been reported in the literature at-least once in an individual affected with sporadic and/or familial Ovarian Cancer (Minucci_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (VUS, n=3; benign/likely benign, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
|
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Uncertain significance
(Jul 29, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001472820.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The BRCA1 c.3362A>G; p.Asn1121Ser variant (rs80356919) is reported in the literature in an individual affected with ovarian cancer, but without a clear disease association (Minucci … (more)
The BRCA1 c.3362A>G; p.Asn1121Ser variant (rs80356919) is reported in the literature in an individual affected with ovarian cancer, but without a clear disease association (Minucci 2015). This variant is reported in ClinVar (Variation ID: 37527), and is only observed on four alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The asparagine at codon 1121 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Additionally, a multifactorial likelihood analysis categorized this variant as likely benign (Parsons 2019). However, given the lack of clinical and functional data, the significance of the p.Asn1121Ser variant is uncertain at this time. References: Minucci A et al. Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: the experience at Gemelli hospital and a literature review. Expert Rev Mol Diagn. 2015;15(10):1383-1403. Parsons MT et al. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. Hum Mutat. 2019;40(9):1557-1578. (less)
|
|
|
Uncertain significance
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025958.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 2
Geographic origin: South Africa
Testing laboratory: National Health Laboratory Service (NHLS)
|
|
|
Uncertain significance
(Sep 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000489351.2
First in ClinVar: May 27, 2015 Last updated: Dec 24, 2022 |
|
|
|
Uncertain significance
(Sep 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV004228139.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
|
|
|
Likely benign
(Oct 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076179.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Feb 05, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000660972.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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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Uncertain significance
(Nov 25, 2004)
|
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: SCV000144739.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Latin American, Caribbean
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Benign
(Feb 24, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000053704.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Comment:
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26306726, 31131967)
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
Variant summary: BRCA1 c.3362A>G (p.Asn1121Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250354 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3362A>G has been reported in the literature at-least once in an individual affected with sporadic and/or familial Ovarian Cancer (Minucci_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (VUS, n=3; benign/likely benign, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
The BRCA1 c.3362A>G; p.Asn1121Ser variant (rs80356919) is reported in the literature in an individual affected with ovarian cancer, but without a clear disease association (Minucci 2015). This variant is reported in ClinVar (Variation ID: 37527), and is only observed on four alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The asparagine at codon 1121 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Additionally, a multifactorial likelihood analysis categorized this variant as likely benign (Parsons 2019). However, given the lack of clinical and functional data, the significance of the p.Asn1121Ser variant is uncertain at this time. References: Minucci A et al. Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: the experience at Gemelli hospital and a literature review. Expert Rev Mol Diagn. 2015;15(10):1383-1403. Parsons MT et al. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. Hum Mutat. 2019;40(9):1557-1578.
Comment:
This alteration is classified as 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.
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, the variant has been reported in an individual with ovarian cancer (PMID: 26306726 (2015)). A multifactorial analysis study has reported that this variant is likely not pathogenic (PMID: 31131967 (2019)). The frequency of this variant in the general population, 0.000016 (4/250354 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26306726, 31131967)
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
Variant summary: BRCA1 c.3362A>G (p.Asn1121Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250354 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3362A>G has been reported in the literature at-least once in an individual affected with sporadic and/or familial Ovarian Cancer (Minucci_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (VUS, n=3; benign/likely benign, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
The BRCA1 c.3362A>G; p.Asn1121Ser variant (rs80356919) is reported in the literature in an individual affected with ovarian cancer, but without a clear disease association (Minucci 2015). This variant is reported in ClinVar (Variation ID: 37527), and is only observed on four alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The asparagine at codon 1121 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Additionally, a multifactorial likelihood analysis categorized this variant as likely benign (Parsons 2019). However, given the lack of clinical and functional data, the significance of the p.Asn1121Ser variant is uncertain at this time. References: Minucci A et al. Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: the experience at Gemelli hospital and a literature review. Expert Rev Mol Diagn. 2015;15(10):1383-1403. Parsons MT et al. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. Hum Mutat. 2019;40(9):1557-1578.
Comment:
This alteration is classified as 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
| Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
| 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 |
| Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: the experience at Gemelli hospital and a literature review. | Minucci A | Expert review of molecular diagnostics | 2015 | PMID: 26306726 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Text-mined citations for rs80356919 ...
HelpThese citations are identified by LitVar using
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.