Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000585027 | SCV000692657 | uncertain significance | not provided | 2017-10-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001335897 | SCV001529153 | uncertain significance | Microcephaly 5, primary, autosomal recessive | 2018-06-13 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Labcorp Genetics |
RCV000585027 | SCV002189952 | uncertain significance | not provided | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 942 of the ASPM protein (p.Arg942Cys). This variant is present in population databases (rs546095187, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ASPM-related conditions. ClinVar contains an entry for this variant (Variation ID: 493058). 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 ASPM 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. |
| Victorian Clinical Genetics Services, |
RCV001335897 | SCV002768275 | uncertain significance | Microcephaly 5, primary, autosomal recessive | 2020-07-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. Disease-associated missense variants in this gene are rare but they have been reported (ClinVar, PMIDs: 20978018, 28004384). (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine (exon 10). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD v2 <0.01 for a recessive condition (13 heterozygotes, 0 homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (p.(Arg942Cys), 10 heterozygote, 0 homozygotes). (N) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (P) 0600 - Variant is located in an annotated domain or motif (Calponin-homology 1; PDB) (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance once (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| Genome- |
RCV001335897 | SCV004178711 | uncertain significance | Microcephaly 5, primary, autosomal recessive | 2023-04-11 | criteria provided, single submitter | clinical testing |