ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.449A>C (p.His150Pro)

dbSNP: rs397507722
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000560952 SCV000661357 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-12 criteria provided, single submitter clinical testing The p.H150P variant (also known as c.449A>C), located in coding exon 4 of the BRCA2 gene, results from an A to C substitution at nucleotide position 449. The histidine at codon 150 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6486 samples (12972 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001327057 SCV001518117 uncertain significance Hereditary breast ovarian cancer syndrome 2020-04-28 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 150 of the BRCA2 protein (p.His150Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 479349). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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