ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.377G>A (p.Arg126Gln)

gnomAD frequency: 0.00001  dbSNP: rs864622549
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000584220 SCV000688265 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-16 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 126 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 2/251460 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002232713 SCV000819288 uncertain significance Juvenile polyposis syndrome 2024-05-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 126 of the BMPR1A protein (p.Arg126Gln). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 490994). 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 with a negative predictive value of 80%. 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 RCV000584220 SCV001182695 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-01 criteria provided, single submitter clinical testing The p.R126Q variant (also known as c.377G>A), located in coding exon 4 of the BMPR1A gene, results from a G to A substitution at nucleotide position 377. The arginine at codon 126 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003471928 SCV004210950 uncertain significance Polyposis syndrome, hereditary mixed, 2 2024-03-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV002232713 SCV004842848 uncertain significance Juvenile polyposis syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 126 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 2/251460 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.

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