ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.94G>C (p.Gly32Arg) (rs755462552)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461457 SCV000552893 uncertain significance Juvenile polyposis syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 32 of the BMPR1A protein (p.Gly32Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs755462552, ExAC 0.003%). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 411643). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 2017-03-30 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.94G>C at the cDNA level, p.Gly32Arg (G32R) at the protein level, and results in the change of a Glycine to an Arginine (GGC>CGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Gly32Arg was not observed at a significant frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glycine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BMPR1A Gly32Arg occurs at a position that is conserved in mammals and is located in the MH1 domain (Howe 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BMPR1A Gly32Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000572168 SCV000668288 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000572168 SCV000682923 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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