rs571718677
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000400.4(ERCC2):c.284A>G(p.Glu95Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000537 in 1,614,046 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 15 hom. )
Consequence
ERCC2
NM_000400.4 missense
NM_000400.4 missense
Scores
12
6
Clinical Significance
Conservation
PhyloP100: 4.14
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009980142).
BP6
?
Variant 19-45368706-T-C is Benign according to our data. Variant chr19-45368706-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 134112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45368706-T-C is described in Lovd as [Benign]. Variant chr19-45368706-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000322 (49/152340) while in subpopulation SAS AF= 0.00952 (46/4832). AF 95% confidence interval is 0.00733. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC2 | NM_000400.4 | c.284A>G | p.Glu95Gly | missense_variant | 5/23 | ENST00000391945.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC2 | ENST00000391945.10 | c.284A>G | p.Glu95Gly | missense_variant | 5/23 | 1 | NM_000400.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00118 AC: 296AN: 250658Hom.: 4 AF XY: 0.00170 AC XY: 230AN XY: 135582
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GnomAD4 exome AF: 0.000560 AC: 818AN: 1461706Hom.: 15 Cov.: 31 AF XY: 0.000831 AC XY: 604AN XY: 727136
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | ERCC2: BS2 - |
not specified Benign:1Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Xeroderma pigmentosum Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 01, 2021 | - - |
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 | May 13, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;T;T;.;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;.;.
REVEL
Uncertain
Sift
Benign
T;T;.;T;.;.
Sift4G
Benign
T;T;T;T;.;T
Polyphen
B;B;.;.;.;.
Vest4
MutPred
Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at