Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480897 | SCV000564706 | uncertain significance | not provided | 2017-03-09 | criteria provided, single submitter | clinical testing | The N257D variant in the BMPR1B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N257D variant is observed in 2/6602 (0.03%) alleles from individuals of Finnish background in the ExAC dataset (Lek et al., 2016). The N257D variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N257D as a variant of uncertain significance, which may be related to the reported brachydactyly in this individual. |
Labcorp Genetics |
RCV001865422 | SCV002260347 | uncertain significance | Type A2 brachydactyly; Acromesomelic dysplasia 3 | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 257 of the BMPR1B protein (p.Asn257Asp). This variant is present in population databases (rs201034260, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BMPR1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 418063). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BMPR1B protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002525753 | SCV003620718 | uncertain significance | Inborn genetic diseases | 2021-06-21 | criteria provided, single submitter | clinical testing | The c.769A>G (p.N257D) alteration is located in exon 9 (coding exon 6) of the BMPR1B gene. This alteration results from a A to G substitution at nucleotide position 769, causing the asparagine (N) at amino acid position 257 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |