ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5152+20T>A (rs376836050)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119141 SCV000153856 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000123931 SCV000167318 benign not specified 2014-05-09 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.
Ambry Genetics RCV000130822 SCV000185718 likely benign Hereditary cancer-predisposing syndrome 2013-12-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Counsyl RCV000411645 SCV000487762 likely benign Breast-ovarian cancer, familial 1 2016-06-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130822 SCV000683260 benign Hereditary cancer-predisposing syndrome 2015-10-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000123931 SCV000918724 benign not specified 2019-06-20 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5152+20T>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 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 0.00016 in 250844 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (0.00016 vs 0.001), allowing no conclusion about variant significance. c.5152+20T>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Wagner_1999), however in one case the variant was present in both an affected and unaffected family member, which provides supporting evidence for a benign role of this variant, although the age of the family members was not provided (Mohammadi_2009). Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.7235insG via UMD; BRCA1 c.68_69delAG from an internal specimen; and BRCA1 c.5152+2T>G from an internal specimen), providing supporting evidence for a benign role. Additionally, the variant has been reported in our lab in a patient as homozygous. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as a benign variant.
Mendelics RCV000411645 SCV001140485 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV001689666 SCV001905997 likely benign not provided no assertion criteria provided clinical testing

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