NM_000124.4(ERCC6):c.2599-26A>G AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 24, 2024
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:: RCV001236817.7

Allele description [Variation Report for NM_000124.4(ERCC6):c.2599-26A>G]

NM_000124.4(ERCC6):c.2599-26A>G

Gene:

ERCC6:ERCC excision repair 6, chromatin remodeling factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q11.23

Genomic location:

Preferred name:

NM_000124.4(ERCC6):c.2599-26A>G

HGVS:

NC_000010.11:g.49473613T>C
NG_009442.1:g.70489A>G
NM_000124.4:c.2599-26A>GMANE SELECT
NM_001346440.2:c.2599-26A>G
LRG_465t1:c.2599-26A>G
LRG_465:g.70489A>G
NC_000010.10:g.50681659T>C
NM_000124.2:c.2599-26A>G
NM_000124.3:c.2599-26A>G

Links:

dbSNP: rs4253196

NCBI 1000 Genomes Browser:

rs4253196

Molecular consequence:

NM_000124.4:c.2599-26A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001346440.2:c.2599-26A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001409554	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 24, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19894250, 27004399, 9443879, 29572252, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001409554

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 24, 2024)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome.

Laugel V, Dalloz C, Durand M, Sauvanaud F, Kristensen U, Vincent MC, Pasquier L, Odent S, Cormier-Daire V, Gener B, Tobias ES, Tolmie JL, Martin-Coignard D, Drouin-Garraud V, Heron D, Journel H, Raffo E, Vigneron J, Lyonnet S, Murday V, Gubser-Mercati D, Funalot B, et al.

Hum Mutat. 2010 Feb;31(2):113-26. doi: 10.1002/humu.21154.

PubMed [citation]

PMID:: 19894250

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing.

Calmels N, Greff G, Obringer C, Kempf N, Gasnier C, Tarabeux J, Miguet M, Baujat G, Bessis D, Bretones P, Cavau A, Digeon B, Doco-Fenzy M, Doray B, Feillet F, Gardeazabal J, Gener B, Julia S, Llano-Rivas I, Mazur A, Michot C, Renaldo-Robin F, et al.

Orphanet J Rare Dis. 2016 Mar 22;11:26. doi: 10.1186/s13023-016-0408-0.

PubMed [citation]

PMID:: 27004399
PMCID:: PMC4804614

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001409554.6

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

Description

This sequence change falls in intron 13 of the ERCC6 gene. It does not directly change the encoded amino acid sequence of the ERCC6 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs4253196, gnomAD 0.01%). This variant has been observed in individual(s) with Cockayne syndrome (PMID: 19894250, 27004399, 29572252). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 190162). Studies have shown that this variant results in partial insertion of intron 13 into the mRNA, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 9443879, 29572252). 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 25, 2025

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