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NM_000400.4(ERCC2):c.816-2A>G AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 27, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002535637.3

Allele description [Variation Report for NM_000400.4(ERCC2):c.816-2A>G]

NM_000400.4(ERCC2):c.816-2A>G

Gene:
ERCC2:ERCC excision repair 2, TFIIH core complex helicase subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.32
Genomic location:
Preferred name:
NM_000400.4(ERCC2):c.816-2A>G
HGVS:
  • NC_000019.10:g.45364121T>C
  • NG_007067.2:g.11467A>G
  • NM_000400.4:c.816-2A>GMANE SELECT
  • NM_001130867.2:c.744-2A>G
  • LRG_461t1:c.816-2A>G
  • LRG_461:g.11467A>G
  • NC_000019.9:g.45867379T>C
  • NM_000400.3:c.816-2A>G
Links:
dbSNP: rs746795177
NCBI 1000 Genomes Browser:
rs746795177
Molecular consequence:
  • NM_000400.4:c.816-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001130867.2:c.744-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003291868Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 27, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene.

Taylor EM, Broughton BC, Botta E, Stefanini M, Sarasin A, Jaspers NG, Fawcett H, Harcourt SA, Arlett CF, Lehmann AR.

Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8658-63.

PubMed [citation]
PMID:
9238033
PMCID:
PMC23065
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003291868.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects an acceptor splice site in intron 9 of the ERCC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ERCC2 are known to be pathogenic (PMID: 9238033, 11335038, 19085937, 19934020). This variant is present in population databases (rs746795177, gnomAD 0.01%). Disruption of this splice site has been observed in individuals with xeroderma pigmentosum (PMID: 26884178). ClinVar contains an entry for this variant (Variation ID: 631814). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024