rs886054500
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000400.4(ERCC2):c.68_70delCCT(p.Ser23del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000400.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250962Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135802
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461058Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 726828
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
ERCC2-related disorder Uncertain:1
The ERCC2 c.68_70delCCT (p.Ser23del) variant has been reported in one study and was found in one individual with trichothiodystrophy in a compound heterozygous state with a second known pathogenic variant (Usuda et al. 2011). Functional studies measuring ultraviolet sensitivity in XP6BE cells demonstrated that the cells expressing the p.Ser23del variant were much more sensitive to UV light than cells expressing the wild type, suggesting that this variant affects the function of ERCC2. Frequency information for this variant is not available in the 1000 Genomes Project, the Exome Sequencing Project or the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Ser23del variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for ERCC2-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
not provided Uncertain:1
This variant, c.68_70del, results in the deletion of 1 amino acid(s) of the ERCC2 protein (p.Ser23del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has been observed in individual(s) with trichothiodystrophy (PMID: 20944642). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 329531). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at