Submissions for variant NM_004329.3(BMPR1A):c.785T>C (p.Val262Ala)

dbSNP: rs770830310

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000466256	SCV000552848	uncertain significance	Juvenile polyposis syndrome	2025-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 262 of the BMPR1A protein (p.Val262Ala). This variant is not present in population databases (gnomAD no frequency). 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: 411617). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Ambry Genetics	RCV000573612	SCV000668317	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-01	criteria provided, single submitter	clinical testing	The p.V262A variant (also known as c.785T>C), located in coding exon 7 of the BMPR1A gene, results from a T to C substitution at nucleotide position 785. The valine at codon 262 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV000679550	SCV000806610	uncertain significance	not provided	2018-01-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679550	SCV000887613	uncertain significance	not provided	2018-08-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000573612	SCV000911563	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-15	criteria provided, single submitter	clinical testing	This missense variant replaces valine with alanine at codon 262 of the BMPR1A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 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.
GeneDx	RCV000679550	SCV002525428	uncertain significance	not provided	2022-05-31	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000679550	SCV004563495	uncertain significance	not provided	2023-10-16	criteria provided, single submitter	clinical testing	The BMPR1A c.785T>C; p.Val262Ala variant (rs770830310), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 411617). This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.9). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time.
All of Us Research Program, National Institutes of Health	RCV000466256	SCV004835944	uncertain significance	Juvenile polyposis syndrome	2024-01-11	criteria provided, single submitter	clinical testing	This missense variant replaces valine with alanine at codon 262 of the BMPR1A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 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.