Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000793746 | SCV000933115 | uncertain significance | Hoyeraal-Hreidarsson syndrome; Autosomal recessive dyskeratosis congenita | 2022-10-05 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 640672). This variant has not been reported in the literature in individuals affected with DCLRE1B-related conditions. This variant is present in population databases (rs202133913, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 418 of the DCLRE1B protein (p.Ser418Phe). |
Ambry Genetics | RCV003279066 | SCV003958941 | uncertain significance | Inborn genetic diseases | 2023-03-21 | criteria provided, single submitter | clinical testing | The c.1253C>T (p.S418F) alteration is located in exon 4 (coding exon 4) of the DCLRE1B gene. This alteration results from a C to T substitution at nucleotide position 1253, causing the serine (S) at amino acid position 418 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |