ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6439C>T (p.His2147Tyr)

dbSNP: rs587781476
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129424 SCV000184194 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-22 criteria provided, single submitter clinical testing The p.H2147Y variant (also known as c.6439C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 6439. The histidine at codon 2147 is replaced by tyrosine, an amino acid with similar properties. 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.
GeneDx RCV000480281 SCV000571355 uncertain significance not provided 2021-11-22 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Also known as 6667C>T; This variant is associated with the following publications: (PMID: 27150160)
Labcorp Genetics (formerly Invitae), Labcorp RCV000545796 SCV000635509 uncertain significance Hereditary breast ovarian cancer syndrome 2023-07-16 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 141075). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 2147 of the BRCA2 protein (p.His2147Tyr).
Color Diagnostics, LLC DBA Color Health RCV000129424 SCV000906140 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-20 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 2147 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000129424 SCV003852526 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).
All of Us Research Program, National Institutes of Health RCV004804130 SCV004844262 uncertain significance BRCA2-related cancer predisposition 2024-06-11 criteria provided, single submitter clinical testing This missense variant replaces histidine with tyrosine at codon 2147 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders 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.
True Health Diagnostics RCV000129424 SCV000787941 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-30 no assertion criteria provided clinical testing

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