Submissions for variant NM_001203.3(BMPR1B):c.11G>A (p.Arg4Gln)

gnomAD frequency: 0.00026  dbSNP: rs150974461

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001155861	SCV001317326	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001220771	SCV001392782	likely benign	Type A2 brachydactyly; Acromesomelic dysplasia 3	2024-01-22	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001334871	SCV001527852	uncertain significance	Acromesomelic dysplasia 3	2018-06-06	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Johns Hopkins Genomics, Johns Hopkins University	RCV001683739	SCV001905478	likely benign	Idiopathic pulmonary arterial hypertension	2021-08-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001776122	SCV002013893	uncertain significance	not provided	2019-07-12	criteria provided, single submitter	clinical testing	Reported in an abstract in patients with primary ovarian insufficiency; no other details aee available to GeneDx (Rossetti et al., 2009); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
PreventionGenetics, part of Exact Sciences	RCV004754696	SCV005364499	uncertain significance	BMPR1B-related disorder	2024-07-31	no assertion criteria provided	clinical testing	The BMPR1B c.11G>A variant is predicted to result in the amino acid substitution p.Arg4Gln. This variant has been reported as uncertain in an individual with primary ovarian insufficiency (reported as p.Arg34Gln in Table S7, Heddar. et al 2022. PubMed ID: 36099812). This variant is reported in 0.062% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, this variant has been reported as benign/likely benign/uncertain (https://preview.ncbi.nlm.nih.gov/clinvar/variation/906582/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.