Submissions for variant NM_004329.3(BMPR1A):c.1140C>T (p.Asp380=)

gnomAD frequency: 0.01512  dbSNP: rs35572415

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001507163	SCV000153827	benign	Juvenile polyposis syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131546	SCV000186545	benign	Hereditary cancer-predisposing syndrome	2014-11-21	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Illumina Laboratory Services, Illumina	RCV001080583	SCV000365651	benign	Generalized juvenile polyposis/juvenile polyposis coli	2018-01-12	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.
Color Diagnostics, LLC DBA Color Health	RCV000131546	SCV000537376	benign	Hereditary cancer-predisposing syndrome	2016-03-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001705875	SCV000602644	benign	not provided	2024-11-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000507545	SCV000806594	benign	not specified	2016-08-12	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000507545	SCV000888816	benign	not specified	2020-08-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001705875	SCV001894507	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000507545	SCV002549929	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001507163	SCV004016726	benign	Juvenile polyposis syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001705875	SCV005317632	benign	not provided		criteria provided, single submitter	not provided
Myriad Genetics, Inc.	RCV001507163	SCV005405383	benign	Juvenile polyposis syndrome	2024-08-06	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000131546	SCV005688950	benign	Hereditary cancer-predisposing syndrome	2025-01-20	criteria provided, single submitter	clinical testing	The synonymous variant NM_004329.3(BMPR1A):c.1140C>T (p.Asp380=) has been reported to ClinVar as Benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 132691 as of 2025-01-02). The variant is observed in one or more well-documented healthy adults. The p.Asp380= variant is not predicted to disrupt an existing splice site. The p.Asp380= variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Benign
True Health Diagnostics	RCV000131546	SCV000787886	likely benign	Hereditary cancer-predisposing syndrome	2018-02-20	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000507545	SCV001553243	benign	not specified		no assertion criteria provided	clinical testing	The BMPR1A p.Asp380= variant was identified in 1 of 96 proband chromosomes (frequency: 0.01) from one individual with Hereditary hemorrhagic telangiectasia; however, the variant is identified as a polymorphism (Lesca 2006). The variant was also identified in the following databases: dbSNP (ID: rs35572415) as "With Likely benign allele", ClinVar (5x benign, 1x likely benign), Clinvitae, and LOVD 3.0 (4x). The variant was not identified in Cosmic or the MutDB database. The variant was identified in control databases in 3968 of 276746 chromosomes (34 homozygous) at a frequency of 0.01 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 92 of 24020 chromosomes (freq: 0.004), Other in 129 of 6460 chromosomes (freq: 0.02), Latino in 477 of 34416 chromosomes (freq: 0.01), European in 2719 of 126260 chromosomes (freq: 0.02), Ashkenazi Jewish in 149 of 10150 chromosomes (freq: 0.01), Finnish in 154 of 25792 chromosomes (freq: 0.006), and South Asian in 248 of 30782 chromosomes (freq: 0.008). The variant was not observed in the East Asian population. A study by Pyatt 2006 investigating Juvenile polyposis syndrome listed this variant as a polymorphism. The p.Asp380= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000507545	SCV001807726	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000507545	SCV001920507	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000507545	SCV001955117	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000507545	SCV002037020	benign	not specified		no assertion criteria provided	clinical testing