Submissions for variant NM_004329.3(BMPR1A):c.961C>T (p.Leu321=)

gnomAD frequency: 0.00011  dbSNP: rs377412651

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163921	SCV000214516	likely benign	Hereditary cancer-predisposing syndrome	2014-10-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV001507227	SCV000288404	benign	Juvenile polyposis syndrome	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000436587	SCV000512266	benign	not specified	2015-04-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000163921	SCV000537479	likely benign	Hereditary cancer-predisposing syndrome	2016-03-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586080	SCV000698328	benign	not provided	2017-07-21	criteria provided, single submitter	clinical testing	Variant summary: The BMPR1A c.961C>T (p.Leu321Leu) variant involves the alteration of a conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may create an ESE binding site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 55/276926 control chromosomes at a frequency of 0.0001986, which is approximately 99 times the estimated maximal expected allele frequency of a pathogenic BMPR1A variant (0.000002), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586080	SCV000885063	likely benign	not provided	2018-01-24	criteria provided, single submitter	clinical testing	The BMPR1A c.961C>T; p.Leu321Leu variant (rs377412651), to our knowledge, is not reported in the medical literature but is reported as benign or likely benign in ClinVar (Variation ID: 184634). This variant is observed in the general population with an overall allele frequency of 0.02% (55/276926 alleles) in the Genome Aggregation Database. This is a synonymous change and computational algorithms do not predict this variant to impact splicing (Alamut v.2.10). Based on available information, this variant is considered likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586080	SCV000887616	benign	not provided	2022-10-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001084234	SCV001263369	benign	Generalized juvenile polyposis/juvenile polyposis coli	2017-06-20	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Genetic Services Laboratory, University of Chicago	RCV000436587	SCV002070272	likely benign	not specified	2021-06-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163921	SCV002531125	benign	Hereditary cancer-predisposing syndrome	2020-12-23	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000436587	SCV004027591	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965200	SCV004776615	likely benign	BMPR1A-related condition	2020-05-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823873	SCV002073616	not provided	Pulmonary arterial hypertension		no assertion provided	literature only