NM_000124.4(ERCC6):c.466C>T (p.Gln156Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 24, 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:: RCV000224212.11

Allele description [Variation Report for NM_000124.4(ERCC6):c.466C>T (p.Gln156Ter)]

NM_000124.4(ERCC6):c.466C>T (p.Gln156Ter)

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.466C>T (p.Gln156Ter)

HGVS:

NC_000010.11:g.49530797G>A
NG_009442.1:g.13305C>T
NM_000124.4:c.466C>TMANE SELECT
NM_001277058.2:c.466C>T
NM_001277059.2:c.466C>T
NM_001346440.2:c.466C>T
NP_000115.1:p.Gln156Ter
NP_001263987.1:p.Gln156Ter
NP_001263988.1:p.Gln156Ter
NP_001333369.1:p.Gln156Ter
LRG_465t1:c.466C>T
LRG_465:g.13305C>T
NC_000010.10:g.50738843G>A
NM_000124.2:c.466C>T
NM_000124.3:c.466C>T
p.Gln156*

Protein change:

Q156*

Links:

dbSNP: rs751838040

NCBI 1000 Genomes Browser:

rs751838040

Molecular consequence:

NM_000124.4:c.466C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001277058.2:c.466C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001277059.2:c.466C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001346440.2:c.466C>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
SCV000280636	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 14, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000329858	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 28, 2023)	germline	clinical testing	Citation Link,
SCV001387855	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 24, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18628313, 19894250, 29572252, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000280636

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 14, 2015)

germline

clinical testing

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

SCV000329858

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 28, 2023)

germline

clinical testing

Citation Link,

SCV001387855

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 24, 2024)

germline

clinical testing

PubMed (4)
[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	not provided	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

Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation.

Laugel V, Dalloz C, Tobias ES, Tolmie JL, Martin-Coignard D, Drouin-Garraud V, Valayannopoulos V, Sarasin A, Dollfus H.

J Med Genet. 2008 Sep;45(9):564-71. doi: 10.1136/jmg.2007.057141. Epub 2008 Jul 15.

PubMed [citation]

PMID:: 18628313

See all PubMed Citations (5)

Details of each submission

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000280636.1

#	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	not provided	not provided	not provided	not provided		not provided	0.000112	not provided	not provided

From GeneDx, SCV000329858.7

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

Description

Nonsense 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: Nikfar2022[article], 33681529, 29572252, 19894250, 34724781)

#	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, SCV001387855.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln156*) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252). This variant is present in population databases (rs751838040, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Cockayne syndrome (PMID: 19894250, 29572252). ClinVar contains an entry for this variant (Variation ID: 212733). 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: Oct 5, 2025

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