NM_005236.3(ERCC4):c.557_558del (p.Phe186fs) AND Xeroderma pigmentosum, group F

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 21, 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:: RCV004555891.1

Allele description [Variation Report for NM_005236.3(ERCC4):c.557_558del (p.Phe186fs)]

NM_005236.3(ERCC4):c.557_558del (p.Phe186fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p13.12

Genomic location:

Preferred name:

NM_005236.3(ERCC4):c.557_558del (p.Phe186fs)

HGVS:

NC_000016.10:g.13926729_13926730del
NG_011442.1:g.11573_11574del
NM_005236.3:c.557_558delMANE SELECT
NP_005227.1:p.Phe186fs
LRG_463:g.11573_11574del
NC_000016.9:g.14020583_14020584del
NC_000016.9:g.14020586_14020587del

Protein change:

F186fs

Links:

dbSNP: rs1419167361

NCBI 1000 Genomes Browser:

rs1419167361

Molecular consequence:

NM_005236.3:c.557_558del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005045029	Clinical Genomics Laboratory, Washington University in St. Louis	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 21, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005045029

Clinical Genomics Laboratory, Washington University in St. Louis

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 21, 2023)

germline

clinical testing

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

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

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

Details of each submission

From Clinical Genomics Laboratory, Washington University in St. Louis, SCV005045029.1

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

Description

The ERCC4 c.557_558del (p.Phe186CysfsTer24) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline pathogenic variant by one submitter. This variant is only observed on 1/251,444 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by deleting two nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely 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: Sep 29, 2024

ClinVar

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