ClinVar Genomic variation as it relates to human health
NM_000400.4(ERCC2):c.335G>A (p.Arg112His)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000400.4(ERCC2):c.335G>A (p.Arg112His)
Variation ID: 16784 Accession: VCV000016784.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.32 19: 45368655 (GRCh38) [ NCBI UCSC ] 19: 45871913 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 8, 2017 Apr 15, 2024 Nov 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000400.4:c.335G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000391.1:p.Arg112His missense NM_001130867.2:c.263G>A NP_001124339.1:p.Arg88His missense NC_000019.10:g.45368655C>T NC_000019.9:g.45871913C>T NG_007067.2:g.6933G>A LRG_461:g.6933G>A LRG_461t1:c.335G>A LRG_461p1:p.Arg112His P18074:p.Arg112His - Protein change
- R112H, R88H
- Other names
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- Canonical SPDI
- NC_000019.10:45368654:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00004
The Genome Aggregation Database (gnomAD) 0.00006
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ERCC2 | - | - |
GRCh38 GRCh37 |
1915 | 1956 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
no assertion criteria provided
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Oct 15, 2001 | RCV000018273.30 | |
Pathogenic (2) |
criteria provided, single submitter
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Jan 28, 2022 | RCV000018274.35 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 10, 2023 | RCV000424822.25 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2023 | RCV003466865.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Xeroderma pigmentosum, group D
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581252.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Mar 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000516727.7
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25795128, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25795128, 12820975, 25897079, 15494306, 18817897, 23232694, 23800062, 12458209, 25431422, 25605938, 10667598, 27982466, 27085493, 27262611, 7920640, 9758621, 25620205, 23221806, 30580289, 33670118) (less)
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Pathogenic
(Aug 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cerebrooculofacioskeletal syndrome 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004194652.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Nov 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001501743.17
First in ClinVar: Mar 14, 2021 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Nov 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002151761.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 112 of the ERCC2 protein (p.Arg112His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 112 of the ERCC2 protein (p.Arg112His). This variant is present in population databases (rs121913020, gnomAD 0.008%). This missense change has been observed in individuals with trichothiodystrophy (PMID: 7920640, 9758621). This variant is also known as a G to A mutation at position 413. ClinVar contains an entry for this variant (Variation ID: 16784). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ERCC2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ERCC2 function (PMID: 25431422). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 15, 2001)
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no assertion criteria provided
Method: literature only
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TRICHOTHIODYSTROPHY 1, PHOTOSENSITIVE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000038552.7
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024 |
Comment on evidence:
Trichothiodystrophy 1, Photosensitive Of 11 reported Italian patients with photosensitive trichothiodystrophy-1 (TTD1; 601675), Botta et al. (1998) noted that 5 were homozygous for an arg112-to-his … (more)
Trichothiodystrophy 1, Photosensitive Of 11 reported Italian patients with photosensitive trichothiodystrophy-1 (TTD1; 601675), Botta et al. (1998) noted that 5 were homozygous for an arg112-to-his (R112H) mutation in the ERCC2 gene and 2 were compound heterozygous. Xeroderma Pigmentosum, Complementation Group D Broughton et al. (2001) described a 28-year-old woman with sun sensitivity, pigmentation changes, and skin cancers typical of xeroderma pigmentosum complementation group D (XPD; 278730). Mutation analysis revealed compound heterozygous mutations in the ERCC2 gene: the R112H mutation and a leu485-to-pro (L485P; 126340.0003) substitution. (less)
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Pathogenic
(Oct 15, 2001)
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no assertion criteria provided
Method: literature only
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XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000038553.7
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024 |
Comment on evidence:
Trichothiodystrophy 1, Photosensitive Of 11 reported Italian patients with photosensitive trichothiodystrophy-1 (TTD1; 601675), Botta et al. (1998) noted that 5 were homozygous for an arg112-to-his … (more)
Trichothiodystrophy 1, Photosensitive Of 11 reported Italian patients with photosensitive trichothiodystrophy-1 (TTD1; 601675), Botta et al. (1998) noted that 5 were homozygous for an arg112-to-his (R112H) mutation in the ERCC2 gene and 2 were compound heterozygous. Xeroderma Pigmentosum, Complementation Group D Broughton et al. (2001) described a 28-year-old woman with sun sensitivity, pigmentation changes, and skin cancers typical of xeroderma pigmentosum complementation group D (XPD; 278730). Mutation analysis revealed compound heterozygous mutations in the ERCC2 gene: the R112H mutation and a leu485-to-pro (L485P; 126340.0003) substitution. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A Drosophila XPD model links cell cycle coordination with neuro-development and suggests links to cancer. | Stettler K | Disease models & mechanisms | 2015 | PMID: 25431422 |
Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. | Broughton BC | Human molecular genetics | 2001 | PMID: 11709541 |
Analysis of mutations in the XPD gene in Italian patients with trichothiodystrophy: site of mutation correlates with repair deficiency, but gene dosage appears to determine clinical severity. | Botta E | American journal of human genetics | 1998 | PMID: 9758621 |
Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy. | Broughton BC | Nature genetics | 1994 | PMID: 7920640 |
Text-mined citations for rs121913020 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.