ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.1049A>T (p.Tyr350Phe)

dbSNP: rs1589291722
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802517 SCV000942352 uncertain significance Juvenile polyposis syndrome 2024-04-10 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 350 of the BMPR1A protein (p.Tyr350Phe). 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: 647896). 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.
Ambry Genetics RCV002388490 SCV002703914 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-18 criteria provided, single submitter clinical testing The p.Y350F variant (also known as c.1049A>T), located in coding exon 8 of the BMPR1A gene, results from an A to T substitution at nucleotide position 1049. The tyrosine at codon 350 is replaced by phenylalanine, an amino acid with highly similar properties. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This amino acid position is highly 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.
All of Us Research Program, National Institutes of Health RCV000802517 SCV004825500 uncertain significance Juvenile polyposis syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with phenylalanine at codon 350 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 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.

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