NM_000124.4(ERCC6):c.1398-2A>G AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Dec 13, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001035343.2

Allele description [Variation Report for NM_000124.4(ERCC6):c.1398-2A>G]

NM_000124.4(ERCC6):c.1398-2A>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.1398-2A>G
HGVS:
  • NC_000010.11:g.49506014T>C
  • NG_009442.1:g.38088A>G
  • NM_000124.4:c.1398-2A>GMANE SELECT
  • NM_001346440.2:c.1398-2A>G
  • LRG_465t1:c.1398-2A>G
  • LRG_465:g.38088A>G
  • NC_000010.10:g.50714060T>C
  • NM_000124.2:c.1398-2A>G
  • NM_000124.3:c.1398-2A>G
Links:
dbSNP: rs1317145066
NCBI 1000 Genomes Browser:
rs1317145066
Molecular consequence:
  • NM_000124.4:c.1398-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001346440.2:c.1398-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001198668Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 13, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome.

Mallery DL, Tanganelli B, Colella S, Steingrimsdottir H, van Gool AJ, Troelstra C, Stefanini M, Lehmann AR.

Am J Hum Genet. 1998 Jan;62(1):77-85. Erratum in: Am J Hum Genet 1999 May;64(5):1491.

PubMed [citation]
PMID:
9443879
PMCID:
PMC1376810
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001198668.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 5 of the ERCC6 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ERCC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 554946). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 9443879, 18628313). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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