NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 31, 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:: RCV001049483.8

Allele description [Variation Report for NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser)]

NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser)

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.1728A>T (p.Arg576Ser)

HGVS:

NC_000016.10:g.13935660A>T
NG_011442.1:g.20504A>T
NM_005236.3:c.1728A>TMANE SELECT
NP_005227.1:p.Arg576Ser
NP_005227.1:p.Arg576Ser
LRG_463t1:c.1728A>T
LRG_463:g.20504A>T
LRG_463p1:p.Arg576Ser
NC_000016.9:g.14029517A>T
NM_005236.2:c.1728A>T

Protein change:

R576S

Links:

dbSNP: rs765454246

NCBI 1000 Genomes Browser:

rs765454246

Molecular consequence:

NM_005236.3:c.1728A>T - 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

Recent activity

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Ecto-5'-nucleotidase 2, isoform A [Drosophila melanogaster]
Ecto-5'-nucleotidase 2, isoform A [Drosophila melanogaster]
gi|19922446|ref|NP_611218.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001213532	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 31, 2023)	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

SCV001213532

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 31, 2023)

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, SCV001213532.5

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ERCC4 protein function. ClinVar contains an entry for this variant (Variation ID: 317816). This missense change has been observed in individual(s) with serous cystadenoma of the pancreas (PMID: 28767289). This variant is present in population databases (rs765454246, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 576 of the ERCC4 protein (p.Arg576Ser).

#	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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