NM_000124.4(ERCC6):c.422+1G>C AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 9, 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:: RCV001238124.4

Allele description [Variation Report for NM_000124.4(ERCC6):c.422+1G>C]

NM_000124.4(ERCC6):c.422+1G>C

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.422+1G>C

HGVS:

NC_000010.11:g.49532542C>G
NG_009442.1:g.11560G>C
NM_000124.4:c.422+1G>CMANE SELECT
NM_001277058.2:c.422+1G>C
NM_001277059.2:c.422+1G>C
NM_001346440.2:c.422+1G>C
LRG_465t1:c.422+1G>C
LRG_465:g.11560G>C
NC_000010.10:g.50740588C>G
NM_000124.2:c.422+1G>C
NM_000124.3:c.422+1G>C

Links:

dbSNP: rs1198472093

NCBI 1000 Genomes Browser:

rs1198472093

Molecular consequence:

NM_000124.4:c.422+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001277058.2:c.422+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001277059.2:c.422+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001346440.2:c.422+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001410921	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 9, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 18628313, 29572252, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001410921

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 9, 2023)

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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 (4)

Details of each submission

From Invitae, SCV001410921.5

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 556340). This variant has not been reported in the literature in individuals affected with ERCC6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the ERCC6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252).

#	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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