rs1555775416
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_000400.4(ERCC2):c.2092C>T(p.Gln698*) variant causes a stop gained change involving the alteration of a conserved nucleotide. 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 (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ERCC2
NM_000400.4 stop_gained
NM_000400.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 9.00
Genes affected
ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0837 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-45352307-G-A is Pathogenic according to our data. Variant chr19-45352307-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559886.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45352307-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ERCC2 | NM_000400.4 | c.2092C>T | p.Gln698* | stop_gained | Exon 22 of 23 | ENST00000391945.10 | NP_000391.1 | |
| ERCC2 | XM_011526611.3 | c.2014C>T | p.Gln672* | stop_gained | Exon 21 of 22 | XP_011524913.1 | ||
| ERCC2 | XR_001753633.3 | n.2125C>T | non_coding_transcript_exon_variant | Exon 22 of 24 | ||||
| ERCC2 | XR_007066680.1 | n.2047C>T | non_coding_transcript_exon_variant | Exon 21 of 23 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebrooculofacioskeletal syndrome 2 Pathogenic:1
Jan 09, 2014
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at