rs147972150
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP4_Moderate
The NM_000400.4(ERCC2):āc.47A>Gā(p.Tyr16Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000226 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Y16Y) has been classified as Likely benign.
Frequency
Consequence
NM_000400.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC2 | NM_000400.4 | c.47A>G | p.Tyr16Cys | missense_variant | 2/23 | ENST00000391945.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC2 | ENST00000391945.10 | c.47A>G | p.Tyr16Cys | missense_variant | 2/23 | 1 | NM_000400.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 171AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000386 AC: 97AN: 251072Hom.: 0 AF XY: 0.000272 AC XY: 37AN XY: 135844
GnomAD4 exome AF: 0.000132 AC: 193AN: 1461196Hom.: 0 Cov.: 32 AF XY: 0.000127 AC XY: 92AN XY: 726892
GnomAD4 genome AF: 0.00112 AC: 171AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85AN XY: 74426
ClinVar
Submissions by phenotype
Ovarian cancer Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Xeroderma pigmentosum Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 01, 2021 | - - |
Cerebrooculofacioskeletal syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 05, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Trichothiodystrophy 1, photosensitive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 10, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
ERCC2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 07, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Xeroderma pigmentosum, group D Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
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