NM_000400.4(ERCC2):c.2143C>T (p.Gln715Ter) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 22, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001765013.4

Allele description [Variation Report for NM_000400.4(ERCC2):c.2143C>T (p.Gln715Ter)]

NM_000400.4(ERCC2):c.2143C>T (p.Gln715Ter)

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.2143C>T (p.Gln715Ter)

HGVS:

NC_000019.10:g.45352256G>A
NG_007067.2:g.23332C>T
NM_000400.4:c.2143C>TMANE SELECT
NP_000391.1:p.Gln715Ter
LRG_461t1:c.2143C>T
LRG_461:g.23332C>T
NC_000019.9:g.45855514G>A
NM_000400.3:c.2143C>T

Protein change:

Q715*

Links:

dbSNP: rs774392894

NCBI 1000 Genomes Browser:

rs774392894

Molecular consequence:

NM_000400.4:c.2143C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001989566	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 28, 2019)	germline	clinical testing	Citation Link,
SCV004678974	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9238033, 11335038, 19085937, 19934020, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001989566

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 28, 2019)

germline

clinical testing

Citation Link,

SCV004678974

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Trichothiodystrophy, a transcription syndrome.

Bergmann E, Egly JM.

Trends Genet. 2001 May;17(5):279-86. Review.

PubMed [citation]

PMID:: 11335038

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV001989566.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 9771713, 29625052)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004678974.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1304777). This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. This variant is present in population databases (rs774392894, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln715*) in the ERCC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC2 are known to be pathogenic (PMID: 9238033, 11335038, 19085937, 19934020).

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

Last Updated: Sep 29, 2024

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