ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1217G>A (p.Arg406His) (rs587780107)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000679546 SCV000149734 uncertain significance not provided 2013-10-21 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.1217G>A at the cDNA level, p.Arg406His (R406H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Arg406His was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one positive polar amino acid for another, altering a position that is well conserved throughout evolution and is located in the protein kinase domain per UniProt. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on currently available information, it is unclear whether BMPR1A Arg406His is pathogenic or benign.
Ambry Genetics RCV000561496 SCV000668372 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000635445 SCV000756858 uncertain significance Juvenile polyposis syndrome 2017-11-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 406 of the BMPR1A protein (p.Arg406His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 127899). 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 disruptive, 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.
PreventionGenetics,PreventionGenetics RCV000679546 SCV000806595 uncertain significance not provided 2017-08-25 criteria provided, single submitter clinical testing

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