NM_005236.3(ERCC4):c.2156C>A (p.Thr719Asn) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2021
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:: RCV001964260.5

Allele description [Variation Report for NM_005236.3(ERCC4):c.2156C>A (p.Thr719Asn)]

NM_005236.3(ERCC4):c.2156C>A (p.Thr719Asn)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.12

Genomic location:

Preferred name:

NM_005236.3(ERCC4):c.2156C>A (p.Thr719Asn)

HGVS:

NC_000016.10:g.13947752C>A
NG_011442.1:g.32596C>A
NM_005236.3:c.2156C>AMANE SELECT
NP_005227.1:p.Thr719Asn
LRG_463:g.32596C>A
NC_000016.9:g.14041609C>A

Protein change:

T719N

Links:

dbSNP: rs779096061

NCBI 1000 Genomes Browser:

rs779096061

Molecular consequence:

NM_005236.3:c.2156C>A - missense variant - [Sequence Ontology: SO:0001583]

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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Homo sapiens glutathione peroxidase 2 (gastrointestinal), mRNA (cDNA clone MGC:71978 IMAGE:6668339), complete cds
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002256181	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28767289, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002256181

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

germline

clinical testing

PubMed (2)
[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

Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma.

Shindo K, Yu J, Suenaga M, Fesharakizadeh S, Cho C, Macgregor-Das A, Siddiqui A, Witmer PD, Tamura K, Song TJ, Navarro Almario JA, Brant A, Borges M, Ford M, Barkley T, He J, Weiss MJ, Wolfgang CL, Roberts NJ, Hruban RH, Klein AP, Goggins M.

J Clin Oncol. 2017 Oct 20;35(30):3382-3390. doi: 10.1200/JCO.2017.72.3502. Epub 2017 Aug 2.

PubMed [citation]

PMID:: 28767289
PMCID:: PMC5648172

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002256181.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces threonine with asparagine at codon 719 of the ERCC4 protein (p.Thr719Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs779096061, ExAC 0.009%). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 28767289). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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