ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.324T>C (p.Asn108=) (rs772010158)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000494914 SCV000578893 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02;
Ambry Genetics RCV000163532 SCV000214090 likely benign Hereditary cancer-predisposing syndrome 2014-07-15 criteria provided, single submitter clinical testing
GeneDx RCV000435362 SCV000512331 likely benign not specified 2015-11-04 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000758880 SCV000560356 likely benign not provided 2019-02-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758880 SCV000887785 likely benign not provided 2017-10-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000435362 SCV000918905 likely benign not specified 2018-04-30 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.324T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.8e-05 in 276490 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (1.8e-05 vs 0.00075), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.324T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2, p.Ser871X; BRCA1, p.Gln1395X; BRCA1, p.Gln1756ProfsX74), providing supporting evidence for a benign role. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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