NM_000124.4(ERCC6):c.2569C>T (p.Arg857Ter) AND Cockayne syndrome type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 22, 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:: RCV004576963.3

Allele description [Variation Report for NM_000124.4(ERCC6):c.2569C>T (p.Arg857Ter)]

NM_000124.4(ERCC6):c.2569C>T (p.Arg857Ter)

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.2569C>T (p.Arg857Ter)

HGVS:

NC_000010.11:g.49474056G>A
NG_009442.1:g.70046C>T
NM_000124.4:c.2569C>TMANE SELECT
NM_001346440.2:c.2569C>T
NP_000115.1:p.Arg857Ter
NP_001333369.1:p.Arg857Ter
LRG_465t1:c.2569C>T
LRG_465:g.70046C>T
NC_000010.10:g.50682102G>A
NM_000124.2:c.2569C>T
NM_000124.3:c.2569C>T

Protein change:

R857*

Links:

dbSNP: rs751448793

NCBI 1000 Genomes Browser:

rs751448793

Molecular consequence:

NM_000124.4:c.2569C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001346440.2:c.2569C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cockayne syndrome type 2 (CSB)
Synonyms:: COCKAYNE SYNDROME B; Cockayne syndrome type 2; Cockayne Syndrome, Type II
Identifiers:: MONDO: MONDO:0019570; MedGen: C0751038; Orphanet: 191; OMIM: 133540

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005060940	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005374442	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 22, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005060940

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005374442

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 22, 2024)

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	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV005060940.1

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

Description

The stop-gained variant c.2569C>T (p.Arg857Ter) in the ERCC6 gene has been reported in the heterozygous state in individuals affected with Cockayne syndrome and Cerebrooculofacioskeletal syndrome (Laugel et al., 2010; Laugel et al., 2008). This variant is reported with the allele frequency (0.002%) in the gnomAD Exome. It has been submitted to ClinVar as Pathogenic. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre, SCV005374442.1

#	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: Dec 14, 2025

ClinVar

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