VCV001026850.13 - ClinVar

NM_007294.4(BRCA1):c.442-2A>G

Germline

Classification

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.

(5)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.442-2A>G

Variation ID: 1026850 Accession: VCV001026850.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43099882 (GRCh38) [ NCBI UCSC ] 17: 41251899 (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	Mar 14, 2021	Aug 11, 2024	May 6, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.442-2A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor
NM_001407571.1:c.232-5A>G		intron variant
NM_001407581.1:c.442-2A>G		splice acceptor
NM_001407582.1:c.442-2A>G		splice acceptor
NM_001407583.1:c.442-2A>G		splice acceptor
NM_001407585.1:c.442-2A>G		splice acceptor
NM_001407587.1:c.442-5A>G		intron variant
NM_001407590.1:c.442-5A>G		intron variant
NM_001407591.1:c.442-5A>G		intron variant
NM_001407593.1:c.442-2A>G		splice acceptor
NM_001407594.1:c.442-2A>G		splice acceptor
NM_001407596.1:c.442-2A>G		splice acceptor
NM_001407597.1:c.442-2A>G		splice acceptor
NM_001407598.1:c.442-2A>G		splice acceptor
NM_001407602.1:c.442-2A>G		splice acceptor
NM_001407603.1:c.442-2A>G		splice acceptor
NM_001407605.1:c.442-2A>G		splice acceptor
NM_001407610.1:c.442-5A>G		intron variant
NM_001407611.1:c.442-5A>G		intron variant
NM_001407612.1:c.442-5A>G		intron variant
NM_001407613.1:c.442-5A>G		intron variant
NM_001407614.1:c.442-5A>G		intron variant
NM_001407615.1:c.442-5A>G		intron variant
NM_001407616.1:c.442-2A>G		splice acceptor
NM_001407617.1:c.442-2A>G		splice acceptor
NM_001407618.1:c.442-2A>G		splice acceptor
NM_001407619.1:c.442-2A>G		splice acceptor
NM_001407620.1:c.442-2A>G		splice acceptor
NM_001407621.1:c.442-2A>G		splice acceptor
NM_001407622.1:c.442-2A>G		splice acceptor
NM_001407623.1:c.442-2A>G		splice acceptor
NM_001407624.1:c.442-2A>G		splice acceptor
NM_001407625.1:c.442-2A>G		splice acceptor
NM_001407626.1:c.442-2A>G		splice acceptor
NM_001407627.1:c.442-5A>G		intron variant
NM_001407628.1:c.442-5A>G		intron variant
NM_001407629.1:c.442-5A>G		intron variant
NM_001407630.1:c.442-5A>G		intron variant
NM_001407631.1:c.442-5A>G		intron variant
NM_001407632.1:c.442-5A>G		intron variant
NM_001407633.1:c.442-5A>G		intron variant
NM_001407634.1:c.442-5A>G		intron variant
NM_001407635.1:c.442-5A>G		intron variant
NM_001407636.1:c.442-5A>G		intron variant
NM_001407637.1:c.442-5A>G		intron variant
NM_001407638.1:c.442-5A>G		intron variant
NM_001407639.1:c.442-2A>G		splice acceptor
NM_001407640.1:c.442-2A>G		splice acceptor
NM_001407641.1:c.442-2A>G		splice acceptor
NM_001407642.1:c.442-2A>G		splice acceptor
NM_001407644.1:c.442-5A>G		intron variant
NM_001407645.1:c.442-5A>G		intron variant
NM_001407646.1:c.433-2A>G		splice acceptor
NM_001407647.1:c.433-2A>G		splice acceptor
NM_001407648.1:c.442-2A>G		splice acceptor
NM_001407649.1:c.442-5A>G		intron variant
NM_001407652.1:c.442-2A>G		splice acceptor
NM_001407653.1:c.364-2A>G		splice acceptor
NM_001407654.1:c.364-2A>G		splice acceptor
NM_001407655.1:c.364-2A>G		splice acceptor
NM_001407656.1:c.364-2A>G		splice acceptor
NM_001407657.1:c.364-2A>G		splice acceptor
NM_001407658.1:c.364-2A>G		splice acceptor
NM_001407659.1:c.364-5A>G		intron variant
NM_001407660.1:c.364-5A>G		intron variant
NM_001407661.1:c.364-5A>G		intron variant
NM_001407662.1:c.364-5A>G		intron variant
NM_001407663.1:c.364-2A>G		splice acceptor
NM_001407664.1:c.442-2A>G		splice acceptor
NM_001407665.1:c.442-2A>G		splice acceptor
NM_001407666.1:c.442-2A>G		splice acceptor
NM_001407667.1:c.442-2A>G		splice acceptor
NM_001407668.1:c.442-2A>G		splice acceptor
NM_001407669.1:c.442-2A>G		splice acceptor
NM_001407670.1:c.442-5A>G		intron variant
NM_001407671.1:c.442-5A>G		intron variant
NM_001407672.1:c.442-5A>G		intron variant
NM_001407673.1:c.442-5A>G		intron variant
NM_001407674.1:c.442-2A>G		splice acceptor
NM_001407675.1:c.442-2A>G		splice acceptor
NM_001407676.1:c.442-2A>G		splice acceptor
NM_001407677.1:c.442-2A>G		splice acceptor
NM_001407678.1:c.442-2A>G		splice acceptor
NM_001407679.1:c.442-2A>G		splice acceptor
NM_001407680.1:c.442-2A>G		splice acceptor
NM_001407681.1:c.442-2A>G		splice acceptor
NM_001407682.1:c.442-2A>G		splice acceptor
NM_001407683.1:c.442-2A>G		splice acceptor
NM_001407684.1:c.442-2A>G		splice acceptor
NM_001407685.1:c.442-5A>G		intron variant
NM_001407686.1:c.442-5A>G		intron variant
NM_001407687.1:c.442-5A>G		intron variant
NM_001407688.1:c.442-5A>G		intron variant
NM_001407689.1:c.442-5A>G		intron variant
NM_001407690.1:c.442-5A>G		intron variant
NM_001407691.1:c.442-5A>G		intron variant
NM_001407692.1:c.301-2A>G		splice acceptor
NM_001407694.1:c.301-2A>G		splice acceptor
NM_001407695.1:c.301-2A>G		splice acceptor
NM_001407696.1:c.301-2A>G		splice acceptor
NM_001407697.1:c.301-2A>G		splice acceptor
NM_001407698.1:c.301-2A>G		splice acceptor
NM_001407724.1:c.301-2A>G		splice acceptor
NM_001407725.1:c.301-2A>G		splice acceptor
NM_001407726.1:c.301-2A>G		splice acceptor
NM_001407727.1:c.301-2A>G		splice acceptor
NM_001407728.1:c.301-2A>G		splice acceptor
NM_001407729.1:c.301-2A>G		splice acceptor
NM_001407730.1:c.301-2A>G		splice acceptor
NM_001407731.1:c.301-2A>G		splice acceptor
NM_001407732.1:c.301-2A>G		splice acceptor
NM_001407733.1:c.301-2A>G		splice acceptor
NM_001407734.1:c.301-2A>G		splice acceptor
NM_001407735.1:c.301-2A>G		splice acceptor
NM_001407736.1:c.301-2A>G		splice acceptor
NM_001407737.1:c.301-2A>G		splice acceptor
NM_001407738.1:c.301-2A>G		splice acceptor
NM_001407739.1:c.301-2A>G		splice acceptor
NM_001407740.1:c.301-5A>G		intron variant
NM_001407741.1:c.301-5A>G		intron variant
NM_001407742.1:c.301-5A>G		intron variant
NM_001407743.1:c.301-5A>G		intron variant
NM_001407744.1:c.301-5A>G		intron variant
NM_001407745.1:c.301-5A>G		intron variant
NM_001407746.1:c.301-5A>G		intron variant
NM_001407747.1:c.301-5A>G		intron variant
NM_001407748.1:c.301-5A>G		intron variant
NM_001407749.1:c.301-5A>G		intron variant
NM_001407750.1:c.301-2A>G		splice acceptor
NM_001407751.1:c.301-2A>G		splice acceptor
NM_001407752.1:c.301-2A>G		splice acceptor
NM_001407838.1:c.301-5A>G		intron variant
NM_001407839.1:c.301-5A>G		intron variant
NM_001407841.1:c.301-5A>G		intron variant
NM_001407842.1:c.301-5A>G		intron variant
NM_001407843.1:c.301-5A>G		intron variant
NM_001407844.1:c.301-5A>G		intron variant
NM_001407845.1:c.301-5A>G		intron variant
NM_001407846.1:c.301-5A>G		intron variant
NM_001407847.1:c.301-5A>G		intron variant
NM_001407848.1:c.301-5A>G		intron variant
NM_001407849.1:c.301-5A>G		intron variant
NM_001407850.1:c.301-2A>G		splice acceptor
NM_001407851.1:c.301-2A>G		splice acceptor
NM_001407852.1:c.301-2A>G		splice acceptor
NM_001407853.1:c.232-5A>G		intron variant
NM_001407854.1:c.442-2A>G		splice acceptor
NM_001407858.1:c.442-2A>G		splice acceptor
NM_001407859.1:c.442-2A>G		splice acceptor
NM_001407860.1:c.442-5A>G		intron variant
NM_001407861.1:c.442-5A>G		intron variant
NM_001407862.1:c.364-2A>G		splice acceptor
NM_001407863.1:c.442-2A>G		splice acceptor
NM_001407874.1:c.364-5A>G		intron variant
NM_001407875.1:c.364-5A>G		intron variant
NM_001407879.1:c.232-2A>G		splice acceptor
NM_001407881.1:c.232-2A>G		splice acceptor
NM_001407882.1:c.232-2A>G		splice acceptor
NM_001407884.1:c.232-2A>G		splice acceptor
NM_001407885.1:c.232-2A>G		splice acceptor
NM_001407886.1:c.232-2A>G		splice acceptor
NM_001407887.1:c.232-2A>G		splice acceptor
NM_001407889.1:c.232-2A>G		splice acceptor
NM_001407894.1:c.232-5A>G		intron variant
NM_001407895.1:c.232-5A>G		intron variant
NM_001407896.1:c.232-5A>G		intron variant
NM_001407897.1:c.232-5A>G		intron variant
NM_001407898.1:c.232-5A>G		intron variant
NM_001407899.1:c.232-5A>G		intron variant
NM_001407900.1:c.232-2A>G		splice acceptor
NM_001407902.1:c.232-2A>G		splice acceptor
NM_001407904.1:c.232-2A>G		splice acceptor
NM_001407906.1:c.232-2A>G		splice acceptor
NM_001407907.1:c.232-2A>G		splice acceptor
NM_001407908.1:c.232-2A>G		splice acceptor
NM_001407909.1:c.232-2A>G		splice acceptor
NM_001407910.1:c.232-2A>G		splice acceptor
NM_001407915.1:c.232-5A>G		intron variant
NM_001407916.1:c.232-5A>G		intron variant
NM_001407917.1:c.232-5A>G		intron variant
NM_001407918.1:c.232-5A>G		intron variant
NM_001407919.1:c.442-2A>G		splice acceptor
NM_001407920.1:c.301-2A>G		splice acceptor
NM_001407921.1:c.301-2A>G		splice acceptor
NM_001407922.1:c.301-2A>G		splice acceptor
NM_001407923.1:c.301-2A>G		splice acceptor
NM_001407924.1:c.301-2A>G		splice acceptor
NM_001407925.1:c.301-2A>G		splice acceptor
NM_001407926.1:c.301-2A>G		splice acceptor
NM_001407927.1:c.301-2A>G		splice acceptor
NM_001407928.1:c.301-2A>G		splice acceptor
NM_001407929.1:c.301-2A>G		splice acceptor
NM_001407930.1:c.301-5A>G		intron variant
NM_001407931.1:c.301-5A>G		intron variant
NM_001407932.1:c.301-5A>G		intron variant
NM_001407933.1:c.301-2A>G		splice acceptor
NM_001407934.1:c.301-5A>G		intron variant
NM_001407935.1:c.301-2A>G		splice acceptor
NM_001407936.1:c.301-5A>G		intron variant
NM_001407937.1:c.442-2A>G		splice acceptor
NM_001407938.1:c.442-2A>G		splice acceptor
NM_001407939.1:c.442-2A>G		splice acceptor
NM_001407940.1:c.442-5A>G		intron variant
NM_001407941.1:c.442-5A>G		intron variant
NM_001407942.1:c.301-2A>G		splice acceptor
NM_001407943.1:c.301-5A>G		intron variant
NM_001407944.1:c.301-2A>G		splice acceptor
NM_001407945.1:c.301-2A>G		splice acceptor
NM_001407946.1:c.232-2A>G		splice acceptor
NM_001407947.1:c.232-2A>G		splice acceptor
NM_001407948.1:c.232-2A>G		splice acceptor
NM_001407949.1:c.232-2A>G		splice acceptor
NM_001407950.1:c.232-2A>G		splice acceptor
NM_001407951.1:c.232-2A>G		splice acceptor
NM_001407952.1:c.232-2A>G		splice acceptor
NM_001407953.1:c.232-2A>G		splice acceptor
NM_001407954.1:c.232-5A>G		intron variant
NM_001407955.1:c.232-5A>G		intron variant
NM_001407956.1:c.232-5A>G		intron variant
NM_001407957.1:c.232-2A>G		splice acceptor
NM_001407958.1:c.232-5A>G		intron variant
NM_001407959.1:c.61-2A>G		splice acceptor
NM_001407960.1:c.61-2A>G		splice acceptor
NM_001407962.1:c.61-5A>G		intron variant
NM_001407963.1:c.61-2A>G		splice acceptor
NM_001407964.1:c.301-5A>G		intron variant
NM_001407965.1:c.61-2A>G		splice acceptor
NM_001407966.1:c.-218-5022A>G		intron variant
NM_001407967.1:c.-218-5022A>G		intron variant
NM_001407968.1:c.442-2A>G		splice acceptor
NM_001407969.1:c.442-2A>G		splice acceptor
NM_001407970.1:c.442-2A>G		splice acceptor
NM_001407971.1:c.442-2A>G		splice acceptor
NM_001407972.1:c.442-5A>G		intron variant
NM_001407973.1:c.442-2A>G		splice acceptor
NM_001407974.1:c.442-2A>G		splice acceptor
NM_001407975.1:c.442-2A>G		splice acceptor
NM_001407976.1:c.442-2A>G		splice acceptor
NM_001407977.1:c.442-2A>G		splice acceptor
NM_001407978.1:c.442-2A>G		splice acceptor
NM_001407979.1:c.442-2A>G		splice acceptor
NM_001407980.1:c.442-2A>G		splice acceptor
NM_001407981.1:c.442-2A>G		splice acceptor
NM_001407982.1:c.442-2A>G		splice acceptor
NM_001407983.1:c.442-2A>G		splice acceptor
NM_001407984.1:c.442-5A>G		intron variant
NM_001407985.1:c.442-5A>G		intron variant
NM_001407986.1:c.442-5A>G		intron variant
NM_001407990.1:c.442-2A>G		splice acceptor
NM_001407991.1:c.442-5A>G		intron variant
NM_001407992.1:c.442-5A>G		intron variant
NM_001407993.1:c.442-2A>G		splice acceptor
NM_001408392.1:c.442-5A>G		intron variant
NM_001408396.1:c.442-5A>G		intron variant
NM_001408397.1:c.442-5A>G		intron variant
NM_001408398.1:c.442-5A>G		intron variant
NM_001408399.1:c.442-5A>G		intron variant
NM_001408400.1:c.442-5A>G		intron variant
NM_001408401.1:c.442-5A>G		intron variant
NM_001408402.1:c.442-5A>G		intron variant
NM_001408403.1:c.442-2A>G		splice acceptor
NM_001408404.1:c.442-2A>G		splice acceptor
NM_001408406.1:c.442-2A>G		splice acceptor
NM_001408407.1:c.442-5A>G		intron variant
NM_001408408.1:c.433-2A>G		splice acceptor
NM_001408409.1:c.364-2A>G		splice acceptor
NM_001408410.1:c.301-2A>G		splice acceptor
NM_001408411.1:c.364-2A>G		splice acceptor
NM_001408412.1:c.364-2A>G		splice acceptor
NM_001408413.1:c.364-5A>G		intron variant
NM_001408414.1:c.364-2A>G		splice acceptor
NM_001408415.1:c.364-2A>G		splice acceptor
NM_001408416.1:c.364-5A>G		intron variant
NM_001408418.1:c.442-2A>G		splice acceptor
NM_001408419.1:c.442-2A>G		splice acceptor
NM_001408420.1:c.442-2A>G		splice acceptor
NM_001408421.1:c.442-5A>G		intron variant
NM_001408422.1:c.442-2A>G		splice acceptor
NM_001408423.1:c.442-2A>G		splice acceptor
NM_001408424.1:c.442-5A>G		intron variant
NM_001408425.1:c.442-2A>G		splice acceptor
NM_001408426.1:c.442-2A>G		splice acceptor
NM_001408427.1:c.442-2A>G		splice acceptor
NM_001408428.1:c.442-2A>G		splice acceptor
NM_001408429.1:c.442-2A>G		splice acceptor
NM_001408430.1:c.442-2A>G		splice acceptor
NM_001408431.1:c.442-5A>G		intron variant
NM_001408432.1:c.442-5A>G		intron variant
NM_001408433.1:c.442-5A>G		intron variant
NM_001408434.1:c.442-5A>G		intron variant
NM_001408435.1:c.442-5A>G		intron variant
NM_001408436.1:c.442-2A>G		splice acceptor
NM_001408437.1:c.442-2A>G		splice acceptor
NM_001408438.1:c.442-2A>G		splice acceptor
NM_001408439.1:c.442-2A>G		splice acceptor
NM_001408440.1:c.442-2A>G		splice acceptor
NM_001408441.1:c.442-2A>G		splice acceptor
NM_001408442.1:c.442-2A>G		splice acceptor
NM_001408443.1:c.442-2A>G		splice acceptor
NM_001408444.1:c.442-2A>G		splice acceptor
NM_001408445.1:c.442-5A>G		intron variant
NM_001408446.1:c.442-5A>G		intron variant
NM_001408447.1:c.442-5A>G		intron variant
NM_001408448.1:c.442-5A>G		intron variant
NM_001408450.1:c.442-5A>G		intron variant
NM_001408451.1:c.310-5A>G		intron variant
NM_001408452.1:c.301-2A>G		splice acceptor
NM_001408453.1:c.301-2A>G		splice acceptor
NM_001408454.1:c.301-2A>G		splice acceptor
NM_001408455.1:c.301-2A>G		splice acceptor
NM_001408456.1:c.301-2A>G		splice acceptor
NM_001408457.1:c.301-2A>G		splice acceptor
NM_001408458.1:c.301-2A>G		splice acceptor
NM_001408459.1:c.301-2A>G		splice acceptor
NM_001408460.1:c.301-2A>G		splice acceptor
NM_001408461.1:c.301-2A>G		splice acceptor
NM_001408462.1:c.301-5A>G		intron variant
NM_001408463.1:c.301-5A>G		intron variant
NM_001408464.1:c.301-5A>G		intron variant
NM_001408465.1:c.301-5A>G		intron variant
NM_001408466.1:c.301-2A>G		splice acceptor
NM_001408467.1:c.301-2A>G		splice acceptor
NM_001408468.1:c.301-5A>G		intron variant
NM_001408469.1:c.301-2A>G		splice acceptor
NM_001408470.1:c.301-5A>G		intron variant
NM_001408472.1:c.442-2A>G		splice acceptor
NM_001408473.1:c.442-5A>G		intron variant
NM_001408474.1:c.364-2A>G		splice acceptor
NM_001408475.1:c.364-5A>G		intron variant
NM_001408476.1:c.364-2A>G		splice acceptor
NM_001408478.1:c.232-2A>G		splice acceptor
NM_001408479.1:c.232-2A>G		splice acceptor
NM_001408480.1:c.232-2A>G		splice acceptor
NM_001408481.1:c.232-2A>G		splice acceptor
NM_001408482.1:c.232-2A>G		splice acceptor
NM_001408483.1:c.232-2A>G		splice acceptor
NM_001408484.1:c.232-2A>G		splice acceptor
NM_001408485.1:c.232-2A>G		splice acceptor
NM_001408489.1:c.232-2A>G		splice acceptor
NM_001408490.1:c.232-5A>G		intron variant
NM_001408491.1:c.232-5A>G		intron variant
NM_001408492.1:c.232-2A>G		splice acceptor
NM_001408493.1:c.232-5A>G		intron variant
NM_001408494.1:c.442-2A>G		splice acceptor
NM_001408495.1:c.442-5A>G		intron variant
NM_001408496.1:c.301-2A>G		splice acceptor
NM_001408497.1:c.301-2A>G		splice acceptor
NM_001408498.1:c.301-2A>G		splice acceptor
NM_001408499.1:c.301-2A>G		splice acceptor
NM_001408500.1:c.301-2A>G		splice acceptor
NM_001408501.1:c.301-2A>G		splice acceptor
NM_001408502.1:c.232-2A>G		splice acceptor
NM_001408503.1:c.301-5A>G		intron variant
NM_001408504.1:c.301-5A>G		intron variant
NM_001408505.1:c.301-5A>G		intron variant
NM_001408506.1:c.232-2A>G		splice acceptor
NM_001408507.1:c.232-2A>G		splice acceptor
NM_001408508.1:c.232-5A>G		intron variant
NM_001408509.1:c.232-5A>G		intron variant
NM_001408510.1:c.61-2A>G		splice acceptor
NM_001408511.1:c.301-5A>G		intron variant
NM_001408512.1:c.61-2A>G		splice acceptor
NM_001408513.1:c.232-2A>G		splice acceptor
NM_001408514.1:c.232-2A>G		splice acceptor
NM_007294.3:c.442-2A>G
NM_007297.4:c.301-2A>G		splice acceptor
NM_007298.4:c.442-2A>G		splice acceptor
NM_007299.4:c.442-2A>G		splice acceptor
NM_007300.4:c.442-2A>G		splice acceptor
NC_000017.11:g.43099882T>C
NC_000017.10:g.41251899T>C
NG_005905.2:g.118102A>G
LRG_292:g.118102A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:43099881:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

dbSNP: rs80358155 VarSome

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
Gene	OMIM	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

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.
Hereditary breast ovarian cancer syndrome	Uncertain significance (1)	criteria provided, single submitter	Apr 15, 2023	RCV001327358.13
Breast-ovarian cancer, familial, susceptibility to, 1 Familial cancer of breast Fanconi anemia, complementation group S Pancreatic cancer, susceptibility to, 4	Uncertain significance (1)	criteria provided, single submitter	Feb 7, 2022	RCV002493710.8
Hereditary cancer-predisposing syndrome	Uncertain significance (1)	criteria provided, single submitter	Feb 28, 2024	RCV002329294.9
Breast-ovarian cancer, familial, susceptibility to, 1	Uncertain significance (1)	criteria provided, single submitter	Jan 20, 2024	RCV003462902.2
not specified	Uncertain significance (1)	criteria provided, single submitter	May 6, 2024	RCV004690079.1

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 (Feb 07, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial cancer of breast Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002796365.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Apr 15, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001518432.4 First in ClinVar: Mar 14, 2021 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 24569164‚ 29907814 Comment: In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more) In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 7 (PMID: 24569164). ClinVar contains an entry for this variant (Variation ID: 1026850). Disruption of this splice site has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29907814). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the BRCA1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 1 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. (less)
Uncertain significance (Feb 28, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002629208.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: The c.442-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 6 in the BRCA1 gene. This nucleotide position … (more) The c.442-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 6 in the BRCA1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of one amino acid; however, the exact functional impact of the deleted amino acid is unknown at this time (Ambry internal data). This single amino acid loss is a naturally occurring isoform and may be referred to as Δ8p in some literature (Colombo M et al. Hum Mol Genet. 2014; 23:3666-80). Based on the available evidence, the clinical significance of this alteration remains unclear. (less)
Uncertain significance (Jan 20, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004215186.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Uncertain significance (May 06, 2024)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005185502.1 First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024	Publications: PubMed (1) PubMed: 29907814 Comment: Variant summary: BRCA1 c.442-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing. Several computational tools predict a significant impact on … (more) Variant summary: BRCA1 c.442-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 3' acceptor site. Three predict the variant strengthens a cryptic 3' acceptor site. One predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. A study shows that disruption of this splice site results in activation of a cryptic splice site three bp downstream (PMID 24569164). The variant was absent in 251404 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.442-2A>G has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29907814, 24569164). ClinVar contains an entry for this variant (Variation ID: 1026850). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)

Comment:

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 7 (PMID: 24569164). ClinVar contains an entry for this variant (Variation ID: 1026850). Disruption of this splice site has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29907814). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the BRCA1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 1 amino acid residue(s), but is expected to preserve the integrity of the reading-frame.

Comment:

The c.442-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 6 in the BRCA1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of one amino acid; however, the exact functional impact of the deleted amino acid is unknown at this time (Ambry internal data). This single amino acid loss is a naturally occurring isoform and may be referred to as Δ8p in some literature (Colombo M et al. Hum Mol Genet. 2014; 23:3666-80). Based on the available evidence, the clinical significance of this alteration remains unclear.

Comment:

Variant summary: BRCA1 c.442-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 3' acceptor site. Three predict the variant strengthens a cryptic 3' acceptor site. One predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. A study shows that disruption of this splice site results in activation of a cryptic splice site three bp downstream (PMID 24569164). The variant was absent in 251404 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.442-2A>G has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29907814, 24569164). ClinVar contains an entry for this variant (Variation ID: 1026850). Based on the evidence outlined above, the variant was classified as uncertain significance.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The germline mutational landscape of BRCA1 and BRCA2 in Brazil.	Palmero EI	Scientific reports	2018	PMID: 29907814
Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: a report from the ENIGMA consortium.	Colombo M	Human molecular genetics	2014	PMID: 24569164

Text-mined citations for rs80358155 ...

These 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

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.442-2A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80358155 ...