chr10-49482759-C-CG
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000124.4(ERCC6):c.2096_2097insC(p.Leu700ValfsTer60) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T699T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000124.4 frameshift
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.2096_2097insC | p.Leu700ValfsTer60 | frameshift_variant | 10/21 | ENST00000355832.10 | |
ERCC6 | NM_001346440.2 | c.2096_2097insC | p.Leu700ValfsTer60 | frameshift_variant | 10/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.2096_2097insC | p.Leu700ValfsTer60 | frameshift_variant | 10/21 | 1 | NM_000124.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251328Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135830
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727232
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Cerebrooculofacioskeletal syndrome 1;C0265201:DE SANCTIS-CACCHIONE SYNDROME;C0751038:Cockayne syndrome type 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 20, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 30, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 190159). This premature translational stop signal has been observed in individual(s) with clinical features of Cockayne syndrome (PMID: 28170084). This variant is present in population databases (rs774791374, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Leu700Valfs*60) 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). - |
Cockayne syndrome type 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Claritas Genomics | Sep 07, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at