ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.353G>A (p.Arg118His)

gnomAD frequency: 0.00002  dbSNP: rs80358603
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000044218 SCV000072231 likely benign Hereditary breast ovarian cancer syndrome 2024-01-24 criteria provided, single submitter clinical testing
GeneDx RCV000587352 SCV000210235 likely benign not provided 2019-09-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 12670525, 10923033, 11948123)
Ambry Genetics RCV000164685 SCV000215352 likely benign Hereditary cancer-predisposing syndrome 2019-02-08 criteria provided, single submitter clinical testing 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587352 SCV000600555 uncertain significance not provided 2021-04-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000200972 SCV000694702 uncertain significance not specified 2024-06-24 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.353G>A (p.Arg118His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.2e-05 in 1607598 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (2.2e-05 vs 0.00075), allowing no conclusion about variant significance. c.353G>A has been reported in the literature as a VUS in cohorts of individuals affected with breast/ovarian cancer as well as in settings of esophageal squamous carcinoma (example, Hu_2002, Machakova_2019, Nguyen-Dumont_2020, Santonocito_2020, Ko_2020). In at-least one of these reports, a patient with esophageal squamous carcinoma also harbored a 12bp deletion at codon 174 of the TP53 gene, although the germline or somatic context of this observation was not clearly specified (example, Hu_2002). A loss of the wild-type BRCA2 allele was observed in this patient. 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 publications have been ascertained in the context of this evaluation (PMID: 12670525, 11948123, 31396961, 31409081, 32772980, 32438681, 36605468). ClinVar contains an entry for this variant (Variation ID: 37845). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Diagnostics, LLC DBA Color Health RCV000164685 SCV000903091 likely benign Hereditary cancer-predisposing syndrome 2017-05-09 criteria provided, single submitter clinical testing
Mendelics RCV000587352 SCV001138954 uncertain significance not provided 2022-12-13 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000200972 SCV002550247 likely benign not specified 2024-07-31 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV003607204 SCV002579674 likely benign Familial cancer of breast 2024-02-09 criteria provided, single submitter clinical testing ACMG codes applied following ENIGMA VCEP rules: BP1_STR
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000044218 SCV005205791 likely benign Hereditary breast ovarian cancer syndrome 2024-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031426 SCV000054031 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2008-02-11 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031426 SCV000146639 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 1999-01-15 no assertion criteria provided clinical testing
3DMed Clinical Laboratory Inc RCV000677866 SCV000804027 uncertain significance Malignant tumor of pancreas 2018-05-21 no assertion criteria provided clinical testing

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