ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.305C>G (p.Ala102Gly) (rs80357190)

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Total submissions: 10
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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) RCV000031086 SCV001161499 benign Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000724
Invitae RCV000203639 SCV000076075 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-15 criteria provided, single submitter clinical testing
GeneDx RCV001353922 SCV000209905 likely benign not provided 2019-06-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 18703817, 25814778, 22711857)
Ambry Genetics RCV000166160 SCV000216934 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-26 criteria provided, single submitter clinical testing The p.A102G variant (also known as c.305C>G), located in coding exon 5 of the BRCA1 gene, results from a C to G substitution at nucleotide position 305. The alanine at codon 102 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in conjunction with a pathogenic gross deletion in BRCA1 in a hereditary breast and ovarian cancer family (Palma MD et al. Cancer Res. 2008 Sep 1;68(17):7006-14). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000048062 SCV000699001 uncertain significance not specified 2019-01-30 criteria provided, single submitter clinical testing Variant summary: The variant, BRCA1 c.305C>G (p.Ala102Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 245488 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.305C>G has been reported in the literature in individuals affected with Breast cancer and ovarian cancer ((Alsop_2012, Palma_2008)). However, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variants have been reported (BRCA1 Del exons 8-9), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as VUS- Possibly Benign.
Color Health, Inc RCV000166160 SCV000903872 likely benign Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001659804 SCV001878120 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031086 SCV000053682 likely benign Breast-ovarian cancer, familial 1 2012-07-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031086 SCV000144993 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353922 SCV000591258 uncertain significance not provided no assertion criteria provided clinical testing

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