NM_000122.2(ERCC3):c.1421dup (p.Asp474fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: May 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000482017.33

Allele description [Variation Report for NM_000122.2(ERCC3):c.1421dup (p.Asp474fs)]

NM_000122.2(ERCC3):c.1421dup (p.Asp474fs)

Gene:

ERCC3:ERCC excision repair 3, TFIIH core complex helicase subunit [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q14.3

Genomic location:

Preferred name:

NM_000122.2(ERCC3):c.1421dup (p.Asp474fs)

HGVS:

NC_000002.12:g.127280553dup
NG_007454.1:g.18624dup
NM_000122.2:c.1421dupMANE SELECT
NM_001303416.2:c.1229dup
NM_001303418.2:c.1229dup
NP_000113.1:p.Asp474fs
NP_001290345.1:p.Asp410fs
NP_001290347.1:p.Asp410fs
LRG_462t1:c.1421dup
LRG_462:g.18624dup
NC_000002.11:g.128038128_128038129insT
NC_000002.11:g.128038129dup
NM_000122.1:c.1421dup
NM_000122.1:c.1421dupA

Protein change:

D410fs

Links:

OMIM: 133510.0006; dbSNP: rs587778281

NCBI 1000 Genomes Browser:

rs587778281

Molecular consequence:

NM_000122.2:c.1421dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001303416.2:c.1229dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001303418.2:c.1229dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566524	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 3, 2023)	germline	clinical testing	Citation Link,
SCV001245707	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (May 1, 2024)	germline	clinical testing	Citation Link,
SCV002241342	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16947863, 28492532
SCV004235169	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 25, 2023)	germline	clinical testing	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	yes	2	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

Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome.

Oh KS, Khan SG, Jaspers NG, Raams A, Ueda T, Lehmann A, Friedmann PS, Emmert S, Gratchev A, Lachlan K, Lucassan A, Baker CC, Kraemer KH.

Hum Mutat. 2006 Nov;27(11):1092-103.

PubMed [citation]

PMID:: 16947863

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000566524.6

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Also known as c.1421_1422insA; This variant is associated with the following publications: (PMID: 26971583, 27356891, 31589614, 30414346, 29625052, 34308104, 24728327, 36451132, 36493725, 16947863)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001245707.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

Description

ERCC3: PVS1, PM2:Supporting

#	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		2	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002241342.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Asp474Glufs*2) in the ERCC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC3 are known to be pathogenic (PMID: 16947863). This variant is present in population databases (rs587778281, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosa (PMID: 16947863). ClinVar contains an entry for this variant (Variation ID: 134130). 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

From Revvity Omics, Revvity, SCV004235169.1

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

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine