NM_005236.3(ERCC4):c.1730dup (p.Tyr577Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 20, 2020
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:: RCV001853034.6

Allele description [Variation Report for NM_005236.3(ERCC4):c.1730dup (p.Tyr577Ter)]

NM_005236.3(ERCC4):c.1730dup (p.Tyr577Ter)

Gene:

ERCC4:ERCC excision repair 4, endonuclease catalytic subunit [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16p13.12

Genomic location:

Preferred name:

NM_005236.3(ERCC4):c.1730dup (p.Tyr577Ter)

HGVS:

NC_000016.10:g.13935662dup
NG_011442.1:g.20506dup
NM_005236.3:c.1730dupMANE SELECT
NP_005227.1:p.Tyr577Ter
NP_005227.1:p.Tyr577Ter
LRG_463t1:c.1730dup
LRG_463:g.20506dup
LRG_463p1:p.Tyr577Ter
NC_000016.9:g.14029518_14029519insA
NC_000016.9:g.14029519dup
NM_005236.2:c.1730dup
NM_005236.3:c.1730dupAMANE SELECT

Protein change:

Y577*

Links:

OMIM: 133520.0009; dbSNP: rs397509404

NCBI 1000 Genomes Browser:

rs397509404

Molecular consequence:

NM_005236.3:c.1730dup - 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
Identifiers:: MONDO: MONDO:0014108; MedGen: C3808988; Orphanet: 84; OMIM: 615272

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236308	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 20, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23623389, 9580660, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236308

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 20, 2020)

germline

clinical testing

PubMed (3)
[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

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

Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.

Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H.

Hum Mol Genet. 1998 Jun;7(6):969-74.

PubMed [citation]

PMID:: 9580660

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236308.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of Cockayne syndrome (PMID: 23623389). ClinVar contains an entry for this variant (Variation ID: 55828). This variant is present in population databases (rs747759202, ExAC 0.006%). 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. Loss-of-function variants in ERCC4 are known to be pathogenic (PMID: 9580660).

#	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: Sep 29, 2024

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