ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9949C>T (p.Leu3317=) (rs777488349)

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Total submissions: 7
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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) RCV000494760 SCV000579090 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 RCV000163907 SCV000214501 likely benign Hereditary cancer-predisposing syndrome 2014-09-11 criteria provided, single submitter clinical testing
Invitae RCV000228048 SCV000283376 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000469115 SCV000541064 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501438 SCV000592308 likely benign not specified 2013-02-22 criteria provided, single submitter clinical testing
Color RCV000163907 SCV000689235 likely benign Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000501438 SCV000918921 likely benign not specified 2018-06-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9949C>T results 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 276918 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.9949C>T 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 likely pathogenic/pathogenic variants have been reported in our internal database (BRCA2 c.9924C>G (p.Tyr3308X), PALB2 c.801_802dupTA (p.Lys268fsX12)), providing supporting evidence for a benign role. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as likely benign.

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