Submissions for variant NM_004329.3(BMPR1A):c.94G>C (p.Gly32Arg)

gnomAD frequency: 0.00002  dbSNP: rs755462552

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461457	SCV000552893	uncertain significance	Juvenile polyposis syndrome	2024-08-01	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 32 of the BMPR1A protein (p.Gly32Arg). This variant is present in population databases (rs755462552, gnomAD 0.002%). 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: 411643). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt BMPR1A function with a negative predictive value of 95%. 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.
GeneDx	RCV000522769	SCV000617152	uncertain significance	not provided	2025-01-16	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV000572168	SCV000668288	benign	Hereditary cancer-predisposing syndrome	2022-04-13	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.
Color Diagnostics, LLC DBA Color Health	RCV000572168	SCV000682923	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-08	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with arginine at codon 32 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 3/251330 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.
CeGaT Center for Human Genetics Tuebingen	RCV000522769	SCV001334624	uncertain significance	not provided	2020-03-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002489081	SCV002779621	uncertain significance	Polyposis syndrome, hereditary mixed, 2; Juvenile polyposis syndrome	2022-04-09	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000461457	SCV004840686	uncertain significance	Juvenile polyposis syndrome	2024-04-16	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with arginine at codon 32 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 3/251330 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	RCV004568076	SCV005058151	uncertain significance	Polyposis syndrome, hereditary mixed, 2	2024-03-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000522769	SCV005624137	uncertain significance	not provided	2024-10-18	criteria provided, single submitter	clinical testing	The BMPR1A c.94G>C (p.Gly32Arg) variant has not been reported in individuals with BMPR1A-related conditions in the published literature. The frequency of this variant in the general population, 0.000026 (3/113630 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.