Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003083989 | SCV003468270 | uncertain significance | Mosaic variegated aneuploidy syndrome 2 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 64 of the CEP57 protein (p.Ser64Asn). This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CEP57-related conditions. ClinVar contains an entry for this variant (Variation ID: 2155856). 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 not expected to disrupt CEP57 protein function with a negative 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 | RCV003072549 | SCV003651407 | uncertain significance | Inborn genetic diseases | 2022-11-09 | criteria provided, single submitter | clinical testing | The c.191G>A (p.S64N) alteration is located in exon 2 (coding exon 2) of the CEP57 gene. This alteration results from a G to A substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 to be replaced by an asparagine (N). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (4/250856) total alleles studied. The highest observed frequency was 0.012% (4/34574) of Latino alleles. This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |