Submissions for variant NM_001203.3(BMPR1B):c.762G>T (p.Arg254Ser)

gnomAD frequency: 0.00001  dbSNP: rs200198618

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000384921	SCV000451661	likely benign	Brachydactyly	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861245	SCV002256692	uncertain significance	Type A2 brachydactyly; Acromesomelic dysplasia 3	2023-06-20	criteria provided, single submitter	clinical testing	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. 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 expected to disrupt BMPR1B protein function. ClinVar contains an entry for this variant (Variation ID: 350120). This variant has not been reported in the literature in individuals affected with BMPR1B-related conditions. This variant is present in population databases (rs200198618, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 254 of the BMPR1B protein (p.Arg254Ser).
Ambry Genetics	RCV004021974	SCV004915275	uncertain significance	Inborn genetic diseases	2021-06-18	criteria provided, single submitter	clinical testing	The c.762G>T (p.R254S) alteration is located in exon 9 (coding exon 6) of the BMPR1B gene. This alteration results from a G to T substitution at nucleotide position 762, causing the arginine (R) at amino acid position 254 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.