ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6532C>A (p.His2178Asn)

dbSNP: rs80358885
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709327 SCV000838841 uncertain significance Hereditary breast ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000113604 SCV001139152 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000709327 SCV001555865 uncertain significance Hereditary breast ovarian cancer syndrome 2021-12-11 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 52123). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This missense change has been observed in individual(s) with BRCA2-related disease (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2178 of the BRCA2 protein (p.His2178Asn).
University of Washington Department of Laboratory Medicine, University of Washington RCV003157314 SCV003847246 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003157314 SCV003855516 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-17 criteria provided, single submitter clinical testing The p.H2178N variant (also known as c.6532C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 6532. The histidine at codon 2178 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV003157314 SCV004362168 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-31 criteria provided, single submitter clinical testing This missense variant replaces histidine with asparagine at codon 2178 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113604 SCV000146877 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2002-05-29 no assertion criteria provided clinical testing
Department of Medical and Surgical Sciences, University of Bologna RCV000113604 SCV004228428 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2023-09-01 no assertion criteria provided clinical testing PM2(Supporting)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)

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