Submissions for variant NM_001200.4(BMP2):c.460C>T (p.Arg154Ter)

dbSNP: rs1057523275

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000428191	SCV000531326	pathogenic	not provided	2024-11-25	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation, as the last 243 amino acid(s) are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37125634, 29198724, 36360260)
SIB Swiss Institute of Bioinformatics	RCV000755726	SCV000883222	likely pathogenic	Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies	2018-10-15	criteria provided, single submitter	curation	This variant is interpreted as Likely Pathogenic, for Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Strong => PVS1 downgraded in strength to Strong (https://www.ncbi.nlm.nih.gov/pubmed/29198724). PM6 => Assumed de novo, but without confirmation of paternity and maternity (https://www.ncbi.nlm.nih.gov/pubmed/29198724).
Blueprint Genetics	RCV000428191	SCV001832404	likely pathogenic	not provided	2019-11-30	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000755726	SCV002044457	pathogenic	Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies	2021-12-17	criteria provided, single submitter	clinical testing	_x000D_Maternally inherited, mother similarly affected Criteria applied: PVS1, PS4_MOD, PS2_SUP, PM2_SUP
Labcorp Genetics (formerly Invitae), Labcorp	RCV000428191	SCV002181347	pathogenic	not provided	2021-03-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg154*) in the BMP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 243 amino acid(s) of the BMP2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of BMP2-related conditions (PMID: 29198724). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 388927). This variant disrupts the C-terminus of the BMP2 protein. Other variant(s) that disrupt this region (p.Cys329*) have been determined to be pathogenic (PMID: 29198724). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000428191	SCV001797887	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000428191	SCV001952600	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000428191	SCV001978735	likely pathogenic	not provided		no assertion criteria provided	clinical testing