19-45352226-C-T
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PM1PM2PM5PP3PP5_Very_Strong
The NM_000400.4(ERCC2):c.2173G>A(p.Ala725Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A725P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000400.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERCC2 | NM_000400.4 | c.2173G>A | p.Ala725Thr | missense_variant | Exon 22 of 23 | ENST00000391945.10 | NP_000391.1 | |
ERCC2 | XM_011526611.3 | c.2095G>A | p.Ala699Thr | missense_variant | Exon 21 of 22 | XP_011524913.1 | ||
ERCC2 | XR_001753633.3 | n.2206G>A | non_coding_transcript_exon_variant | Exon 22 of 24 | ||||
ERCC2 | XR_007066680.1 | n.2128G>A | non_coding_transcript_exon_variant | Exon 21 of 23 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cerebrooculofacioskeletal syndrome 2 Pathogenic:1
- -
not provided Pathogenic:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22617342, 23232694, 20633800) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at