NM_005236.2(ERCC4):c.1731del (p.Arg576_Tyr577insTer) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Mar 28, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000651478.2

Allele description [Variation Report for NM_005236.2(ERCC4):c.1731del (p.Arg576_Tyr577insTer)]

NM_005236.2(ERCC4):c.1731del (p.Arg576_Tyr577insTer)

Gene:
ERCC4:ERCC excision repair 4, endonuclease catalytic subunit [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
16p13.12
Genomic location:
Preferred name:
NM_005236.2(ERCC4):c.1731del (p.Arg576_Tyr577insTer)
HGVS:
  • NC_000016.10:g.13935663del
  • NG_011442.1:g.20507del
  • NM_005236.2:c.1731del
  • NP_005227.1:p.Arg576_Tyr577insTer
  • LRG_463t1:c.1731del
  • LRG_463:g.20507del
  • LRG_463p1:p.Arg576_Tyr577insTer
  • NC_000016.9:g.14029520del
  • NM_005236.2:c.1731delC
Links:
dbSNP: rs1555468482
NCBI 1000 Genomes Browser:
rs1555468482
Molecular consequence:
  • NM_005236.2:c.1731del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Xeroderma pigmentosum, group F (XPF)
Synonyms:
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F; XERODERMA PIGMENTOSUM VI; XP, GROUP F; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010215; MedGen: C0268140; OMIM: 278760
Name:
Cockayne syndrome
Synonyms:
Cockayne's syndrome; Dwarfism-retinal atrophy-deafness syndrome; Progeria-like syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0016006; MedGen: C0009207
Name:
Fanconi anemia, complementation group Q (FANCQ)
Identifiers:
MONDO: MONDO:0014108; MedGen: C3808988; Orphanet: 84; OMIM: 615272

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000773330Invitaecriteria provided, single submitter
Pathogenic
(Mar 28, 2018)
germlineclinical testing

PubMed (2)
[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

Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.

Kashiyama K, Nakazawa Y, Pilz DT, Guo C, Shimada M, Sasaki K, Fawcett H, Wing JF, Lewin SO, Carr L, Li TS, Yoshiura K, Utani A, Hirano A, Yamashita S, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Takahashi Y, et al.

Am J Hum Genet. 2013 May 2;92(5):807-19. doi: 10.1016/j.ajhg.2013.04.007. Epub 2013 Apr 25.

PubMed [citation]
PMID:
23623389
PMCID:
PMC3644632

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000773330.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Tyr577*) in the ERCC4 gene. It is expected to result 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 ERCC4-related disease. A different variant (c.1730_1731insA) giving rise to the same protein effect observed here (p.Tyr577*) has been reported in an individual affected with Cockayne syndrome (PMID: 23623389). Loss-of-function variants in ERCC4 are known to be pathogenic (PMID: 23623386). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Apr 12, 2021

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