rs3916876
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000400.4(ERCC2):c.1737C>T(p.Val579=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000639 in 1,613,878 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V579V) has been classified as Likely benign.
Frequency
Consequence
NM_000400.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC2 | NM_000400.4 | c.1737C>T | p.Val579= | synonymous_variant | 18/23 | ENST00000391945.10 | |
ERCC2 | XM_011526611.3 | c.1659C>T | p.Val553= | synonymous_variant | 17/22 | ||
ERCC2 | XR_001753633.3 | n.1770C>T | non_coding_transcript_exon_variant | 18/24 | |||
ERCC2 | XR_007066680.1 | n.1692C>T | non_coding_transcript_exon_variant | 17/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC2 | ENST00000391945.10 | c.1737C>T | p.Val579= | synonymous_variant | 18/23 | 1 | NM_000400.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00104 AC: 158AN: 151988Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00225 AC: 565AN: 251286Hom.: 5 AF XY: 0.00190 AC XY: 258AN XY: 135844
GnomAD4 exome AF: 0.000598 AC: 874AN: 1461772Hom.: 9 Cov.: 33 AF XY: 0.000562 AC XY: 409AN XY: 727202
GnomAD4 genome ? AF: 0.00104 AC: 158AN: 152106Hom.: 1 Cov.: 32 AF XY: 0.00114 AC XY: 85AN XY: 74360
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ERCC2: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Xeroderma pigmentosum, group D;C1853102:Cerebrooculofacioskeletal syndrome 2;C1866504:Trichothiodystrophy 1, photosensitive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 10, 2022 | - - |
Xeroderma pigmentosum, group D Benign:1
Likely benign, 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at