Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor- |
RCV000087318 | SCV000266532 | pathogenic | Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome | criteria provided, single submitter | research | ||
Invitae | RCV001233915 | SCV001406530 | uncertain significance | not provided | 2023-08-10 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the PCYT1A gene (p.Ser331Profs*166). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the PCYT1A protein and extend the protein by 128 additional amino acid residues. This variant is present in population databases (rs587777193, gnomAD 0.02%). This frameshift has been observed in individual(s) with spondylometaphyseal dysplasia with cone-rod dystrophy (PMID: 24387990). ClinVar contains an entry for this variant (Variation ID: 101061). 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. |
Victorian Clinical Genetics Services, |
RCV000087318 | SCV002767816 | likely pathogenic | Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous deletion variant was identified, NM_005017.3(PCYT1A):c.990delC in exon 10 of 10 of the PCYT1A gene. This deletion is predicted to cause a frameshift starting at position 331, introducing a stop codon 165 residues downstream, NP_005008.2(PCYT1A):p.(Ser331Profs*166). The variant is predicted to result in a loss of normal protein function through an extension of the reading frame, which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD population database at a frequency of 0.007% (19 heterozygotes, 0 homozygotes). It has been previously reported in patients with Spondylometaphyseal dysplasia with cone-rod dystrophy (ClinVar, Hoover-Fong, J. et al. (2014)). Other variants predicted to cause an extension of the reading frame have been reported as pathogenic in individuals with this condition (Payne, F. et al (2014)). Based on information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. |
OMIM | RCV000087318 | SCV000120198 | pathogenic | Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome | 2014-01-02 | no assertion criteria provided | literature only |