Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001352305 | SCV001546851 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 378 of the ERCC6L2 protein (p.Trp378Arg). This variant is present in population databases (rs200807189, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ERCC6L2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1047574). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Genetic Services Laboratory, |
RCV001820049 | SCV002066731 | uncertain significance | not specified | 2021-11-22 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the ERCC6L2 gene demonstrated a sequence change, c.1132T>C, in exon 6 that results in an amino acid change, p.Trp378Arg. This sequence change has been described in the gnomAD database with a frequency of 0.024% in the Latino/admixed American subpopulation (dbSNP rs200807189). The p.Trp378Arg change affects a poorly conserved amino acid residue located in a domain of the ERCC6L2 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Trp378Arg substitution. This sequence change does not appear to have been previously described in individuals with ERCC6L2-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Trp378Arg change remains unknown at this time. |
Fulgent Genetics, |
RCV002504566 | SCV002803830 | uncertain significance | Pancytopenia-developmental delay syndrome | 2022-05-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002547552 | SCV003741476 | uncertain significance | Inborn genetic diseases | 2021-06-22 | criteria provided, single submitter | clinical testing | The c.1132T>C (p.W378R) alteration is located in exon 6 (coding exon 6) of the ERCC6L2 gene. This alteration results from a T to C substitution at nucleotide position 1132, causing the tryptophan (W) at amino acid position 378 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |