Submissions for variant NM_004329.3(BMPR1A):c.1560G>A (p.Thr520=)

gnomAD frequency: 0.00136  dbSNP: rs142775086

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000174534	SCV000167204	benign	not specified	2014-02-26	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.
Ambry Genetics	RCV000123861	SCV000213642	likely benign	Hereditary cancer-predisposing syndrome	2014-10-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Eurofins Ntd Llc (ga)	RCV000174534	SCV000225849	benign	not specified	2015-04-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079281	SCV000261826	benign	Juvenile polyposis syndrome	2024-01-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000123861	SCV000682877	benign	Hereditary cancer-predisposing syndrome	2016-03-09	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000174534	SCV000888822	benign	not specified	2021-11-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000123861	SCV002528582	benign	Hereditary cancer-predisposing syndrome	2020-12-31	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001079281	SCV004016737	benign	Juvenile polyposis syndrome	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001079281	SCV004838522	benign	Juvenile polyposis syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004706556	SCV005221844	likely benign	not provided		criteria provided, single submitter	not provided
Myriad Genetics, Inc.	RCV001079281	SCV005404059	benign	Juvenile polyposis syndrome	2024-08-08	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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000174534	SCV000691805	likely benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356619	SCV001551837	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The BMPR1A p.Thr520= variant was not identified in the literature nor was it identified in the Cosmic or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs142775086) as "With other allele" and ClinVar (classified as benign by GeneDx, Invitae, Color Genomics and two other clinical laboratories; as likely benign by Ambry Genetics and Mayo Clinic). The variant was identified in control databases in 108 of 277220 chromosomes at a frequency of 0.0004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 99 of 24020 chromosomes (freq: 0.004), Latino in 7 of 34420 chromosomes (freq: 0.0002), and South Asian in 2 of 30780 chromosomes (freq: 0.00007); it was not observed in the Other, European, Ashkenazi Jewish, East Asian, or Finnish populations. The p.Thr520= 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, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.