Submissions for variant NM_001199.4(BMP1):c.2110_2111del (p.Lys704fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003860875	SCV004667468	pathogenic	not provided	2023-03-21	criteria provided, single submitter	clinical testing	The BMP1 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001199.3, and corresponds to NM_006129.4:c.2108-683_2108-682del in the primary transcript This sequence change results in a frameshift in the BMP1 gene (p.Lys704Glufs*191). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the BMP1 protein and extend the protein by 163 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BMP1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant results in an extension of the BMP1 protein. Other variant(s) that result in a similarly extended protein product (p.Gln730Profs*?) have been determined to be pathogenic (PMID: 25656619, 27576954). This suggests that these extensions are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.