NM_000400.4(ERCC2):c.1991_1992del (p.Val664fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 25, 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:: RCV003729511.1

Allele description [Variation Report for NM_000400.4(ERCC2):c.1991_1992del (p.Val664fs)]

NM_000400.4(ERCC2):c.1991_1992del (p.Val664fs)

Gene:

ERCC2:ERCC excision repair 2, TFIIH core complex helicase subunit [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_000400.4(ERCC2):c.1991_1992del (p.Val664fs)

HGVS:

NC_000019.10:g.45352561AC[2]
NG_007067.2:g.23023TG[2]
NM_000400.4:c.1991_1992delMANE SELECT
NP_000391.1:p.Val664Glyfs
NP_000391.1:p.Val664fs
LRG_461t1:c.1986_1987GT[2]
LRG_461:g.23023TG[2]
LRG_461p1:p.Val664Glyfs
NC_000019.9:g.45855818_45855819del
NC_000019.9:g.45855819AC[2]
NM_000400.3:c.1986_1987GT[2]

Protein change:

V664fs

Molecular consequence:

NM_000400.4:c.1991_1992del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004532861	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 25, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31282071, 31803976, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004532861

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 25, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel ERCC2 mutation in two siblings with trichothiodystrophy.

Lund EB, Stein SL.

Pediatr Dermatol. 2019 Sep;36(5):668-671. doi: 10.1111/pde.13882. Epub 2019 Jul 8.

PubMed [citation]

PMID:: 31282071

ERCC2 mutations in two siblings with a severe trichothiodystrophy phenotype.

Leemans G, De Raeve L, Keymolen K.

J Eur Acad Dermatol Venereol. 2020 Apr;34(4):876-879. doi: 10.1111/jdv.16134. Epub 2020 Jan 6.

PubMed [citation]

PMID:: 31803976

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004532861.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the ERCC2 gene (p.Val664Glyfs*109). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 97 amino acid(s) of the ERCC2 protein and extend the protein by 11 additional amino acid residues. This variant disrupts a region of the ERCC2 protein in which other variant(s) (p.Arg722Trp ) have been determined to be pathogenic (PMID: 31282071, 31803976). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 28, 2024

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