rs34517175
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBP6BS2
The ENST00000391945.10(ERCC2):c.1904C>T(p.Ala635Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,613,814 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A635A) has been classified as Likely benign.
Frequency
Consequence
ENST00000391945.10 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERCC2 | NM_000400.4 | c.1904C>T | p.Ala635Val | missense_variant, splice_region_variant | 21/23 | ENST00000391945.10 | NP_000391.1 | |
ERCC2 | XM_011526611.3 | c.1826C>T | p.Ala609Val | missense_variant, splice_region_variant | 20/22 | XP_011524913.1 | ||
ERCC2 | XR_001753633.3 | n.1937C>T | splice_region_variant, non_coding_transcript_exon_variant | 21/24 | ||||
ERCC2 | XR_007066680.1 | n.1859C>T | splice_region_variant, non_coding_transcript_exon_variant | 20/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERCC2 | ENST00000391945.10 | c.1904C>T | p.Ala635Val | missense_variant, splice_region_variant | 21/23 | 1 | NM_000400.4 | ENSP00000375809 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000651 AC: 99AN: 152166Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00162 AC: 407AN: 250822Hom.: 3 AF XY: 0.00150 AC XY: 204AN XY: 135768
GnomAD4 exome AF: 0.000623 AC: 911AN: 1461648Hom.: 8 Cov.: 37 AF XY: 0.000624 AC XY: 454AN XY: 727150
GnomAD4 genome AF: 0.000651 AC: 99AN: 152166Hom.: 1 Cov.: 32 AF XY: 0.000552 AC XY: 41AN XY: 74328
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ERCC2: PP3, BS1, BS2 - |
Xeroderma pigmentosum, group D Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Xeroderma pigmentosum Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jul 28, 2020 | - - |
ERCC2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at