Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000459864 | SCV000545932 | uncertain significance | Baller-Gerold syndrome | 2025-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 203 of the RECQL4 protein (p.Gly203Glu). This variant is present in population databases (rs776532961, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 406962). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RECQL4 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. |
St. |
RCV001775120 | SCV002012427 | uncertain significance | Rothmund-Thomson syndrome type 2 | 2021-10-20 | criteria provided, single submitter | clinical testing | The RECQL4 c.608G>A (p.Gly203Glu) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/8-145741895-C-T). In silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with RECQL4-associated disorders. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4. |