ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.524G>A (p.Cys175Tyr)

gnomAD frequency: 0.00001  dbSNP: rs370091063
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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 RCV000167415 SCV000218270 benign Hereditary cancer-predisposing syndrome 2022-09-08 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000635417 SCV000756830 uncertain significance Juvenile polyposis syndrome 2023-09-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 175 of the BMPR1A protein (p.Cys175Tyr). This variant is present in population databases (rs370091063, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 187666). 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 BMPR1A protein function. 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.
Color Diagnostics, LLC DBA Color Health RCV000167415 SCV001356690 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-09 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 175 of the BMPR1A 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 BMPR1A-related disorders in the literature. This variant has been identified in 3/250844 chromosomes 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002267923 SCV002550407 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000635417 SCV004842864 uncertain significance Juvenile polyposis syndrome 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 175 of the BMPR1A protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/250844 chromosomes 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.
Baylor Genetics RCV004567349 SCV005058190 uncertain significance Polyposis syndrome, hereditary mixed, 2 2023-12-14 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV004791302 SCV005412162 uncertain significance not provided 2024-04-09 criteria provided, single submitter clinical testing PM2_moderate

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