rs751448793
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000124.4(ERCC6):c.2569C>T(p.Arg857Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000018 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R857R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000124.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC6 | NM_000124.4 | c.2569C>T | p.Arg857Ter | stop_gained | 13/21 | ENST00000355832.10 | |
ERCC6 | NM_001346440.2 | c.2569C>T | p.Arg857Ter | stop_gained | 13/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.2569C>T | p.Arg857Ter | stop_gained | 13/21 | 1 | NM_000124.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251172Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135756
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461714Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727164
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Cerebrooculofacioskeletal syndrome 1;C0265201:DE SANCTIS-CACCHIONE SYNDROME;C0751038:Cockayne syndrome type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Aug 24, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | This sequence change creates a premature translational stop signal (p.Arg857*) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252). This variant is present in population databases (rs751448793, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Cockayne syndrome or cerebrooculofacioskeletal syndrome (PMID: 18628313, 19894250). ClinVar contains an entry for this variant (Variation ID: 553383). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at