NM_000082.4(ERCC8):c.1083G>T (p.Trp361Cys) AND UV-sensitive syndrome 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 14, 2009
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000024268.3

Allele description [Variation Report for NM_000082.4(ERCC8):c.1083G>T (p.Trp361Cys)]

NM_000082.4(ERCC8):c.1083G>T (p.Trp361Cys)

Gene:

ERCC8:ERCC excision repair 8, CSA ubiquitin ligase complex subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q12.1

Genomic location:

Preferred name:

NM_000082.4(ERCC8):c.1083G>T (p.Trp361Cys)

HGVS:

NC_000005.10:g.60887479C>A
NG_009289.1:g.62600G>T
NM_000082.4:c.1083G>TMANE SELECT
NM_001007233.3:c.909G>T
NM_001290285.2:c.624G>T
NP_000073.1:p.Trp361Cys
NP_000073.1:p.Trp361Cys
NP_001007234.1:p.Trp303Cys
NP_001277214.1:p.Trp208Cys
LRG_466t1:c.1083G>T
LRG_466:g.62600G>T
LRG_466p1:p.Trp361Cys
NC_000005.9:g.60183306C>A
NM_000082.3:c.1083G>T
Q13216:p.Trp361Cys

Protein change:

W208C; TRP361CYS

Links:

UniProtKB: Q13216#VAR_068177; UniProtKB/Swiss-Prot: VAR_068177; OMIM: 609412.0006; dbSNP: rs281875221

NCBI 1000 Genomes Browser:

rs281875221

Molecular consequence:

NM_000082.4:c.1083G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001007233.3:c.909G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001290285.2:c.624G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: UV-sensitive syndrome 2 (UVSS2)
Identifiers:: MONDO: MONDO:0013829; MedGen: C3553298; Orphanet: 178338; OMIM: 614621

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Micromonospora chokoriensis strain CR3 16S ribosomal RNA gene, partial sequence
Micromonospora chokoriensis strain CR3 16S ribosomal RNA gene, partial sequence
gi|441431797|gb|KC191703.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045559	OMIM	no assertion criteria provided	Pathogenic (Apr 14, 2009)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000045559

OMIM

no assertion criteria provided

Pathogenic
(Apr 14, 2009)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage.

Nardo T, Oneda R, Spivak G, Vaz B, Mortier L, Thomas P, Orioli D, Laugel V, Stary A, Hanawalt PC, Sarasin A, Stefanini M.

Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6209-14. doi: 10.1073/pnas.0902113106. Epub 2009 Mar 27.

PubMed [citation]

PMID:: 19329487
PMCID:: PMC2667150

Details of each submission

From OMIM, SCV000045559.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 15-year-old French girl with UV-sensitive syndrome-2 (UVSS2; 614621), Nardo et al. (2009) identified a homozygous 1083G-T transversion in the ERCC8 gene, resulting in a trp361-to-cys (W361C) substitution within the last putative WD domain. Her unaffected mother was heterozygous for the mutation. Patient-derived fibroblasts showed a reduced recovery of RNA synthesis after UV irradiation and a defective capacity to repair UV-induced damage on the transcribed strand of active genes, indicating a defect in transcription-coupled nucleotide excision repair (TC-NER). However, there was no hypersensitivity to reactive oxygen species, and UV-induced DNA repair synthesis and global genome NER (GG-NER) were normal. Transfection of the construct expressing the mutant protein into normal cells caused a defect in RNA synthesis after UV irradiation. The patient presented at age 4 months with sun sensitivity manifest as easy sun burning and erythema. She had numerous freckles on her face and exposed areas of the neck, but no history or evidence of cutaneous tumors. Psychomotor development was normal. Nardo et al. (2009) hypothesized that the mild phenotype in this patient was due to the lack of cellular sensitivity to oxidative stress.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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