Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000173453 | SCV000224568 | uncertain significance | not provided | 2015-01-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001247524 | SCV001420951 | uncertain significance | Bardet-Biedl syndrome | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 5 of the WDPCP protein (p.Phe5Leu). This variant is present in population databases (rs768802269, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with WDPCP-related conditions. ClinVar contains an entry for this variant (Variation ID: 193387). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002516587 | SCV003691442 | likely benign | Inborn genetic diseases | 2021-11-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV003407639 | SCV004112058 | uncertain significance | WDPCP-related condition | 2023-09-18 | criteria provided, single submitter | clinical testing | The WDPCP c.13T>C variant is predicted to result in the amino acid substitution p.Phe5Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.15% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-63815393-A-G), which is likely too common to be an unreported primary cause of disease. Although we suspect that WDPCP c.13T>C (p.Phe5Leu) may be benign, the clinical significance of this variant is currently classified as uncertain due to the absence of conclusive functional and genetic evidence. |