ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1274A>T (p.Tyr425Phe) (rs758599378)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195582 SCV000254792 uncertain significance Juvenile polyposis syndrome 2018-01-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with phenylalanine at codon 425 of the BMPR1A protein (p.Tyr425Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant is present in population databases (rs758599378, ExAC 0.003%). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 216577). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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.
Ambry Genetics RCV000222403 SCV000273194 uncertain significance Hereditary cancer-predisposing syndrome 2015-12-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000222403 SCV000688234 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-22 criteria provided, single submitter clinical testing
Clinical Cancer Genetics and Family Consultants,Athens Medical Center RCV000222403 SCV000882716 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-07 criteria provided, single submitter clinical testing NM_004329.2:c.1274A>T is a rare variant; frequencies in population databases are: Exome Aggregation Consortium (ExAC)- 0.00002, The Genome Aggregation Database (gnomAD)- 0.00002, Trans-Omics for Precision Medicine (TOPMed)- 0.00002. This variant has not been reported in any breast cancer patient in the literature. The impact of this missense change on protein structure and function is not known. Algorithms developed to predict the effect do not agree - (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). There is no sufficient evidence so far for the pathogenicity of this variant.

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