NM_000053.4(ATP7B):c.2448G>T (p.Arg816Ser) AND Wilson disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 23, 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:: RCV001950954.4

Allele description [Variation Report for NM_000053.4(ATP7B):c.2448G>T (p.Arg816Ser)]

NM_000053.4(ATP7B):c.2448G>T (p.Arg816Ser)

Gene:

ATP7B:ATPase copper transporting beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.2448G>T (p.Arg816Ser)

HGVS:

NC_000013.11:g.51950399C>A
NG_008806.1:g.66096G>T
NM_000053.4:c.2448G>TMANE SELECT
NM_001005918.3:c.1962G>T
NM_001243182.2:c.2115G>T
NM_001330578.2:c.2214G>T
NM_001330579.2:c.2196G>T
NP_000044.2:p.Arg816Ser
NP_001005918.1:p.Arg654Ser
NP_001230111.1:p.Arg705Ser
NP_001317507.1:p.Arg738Ser
NP_001317508.1:p.Arg732Ser
NC_000013.10:g.52524535C>A

Protein change:

R654S

Links:

dbSNP: rs1957924589

NCBI 1000 Genomes Browser:

rs1957924589

Molecular consequence:

NM_000053.4:c.2448G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005918.3:c.1962G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.2115G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330578.2:c.2214G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.2196G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Wilson disease (WND)
Synonyms:: Wilson's disease; Hepatolenticular degeneration
Identifiers:: MONDO: MONDO:0010200; MedGen: C0019202; Orphanet: 905; OMIM: 277900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236291	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 23, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22763723, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236291

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 23, 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

Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study.

Hofer H, Willheim-Polli C, Knoflach P, Gabriel C, Vogel W, Trauner M, Müller T, Ferenci P.

J Hum Genet. 2012 Sep;57(9):564-7. doi: 10.1038/jhg.2012.65. Epub 2012 Jul 5. Erratum in: J Hum Genet. 2021 Dec;66(12):1199. doi: 10.1038/s10038-021-00918-w.

PubMed [citation]

PMID:: 22763723

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, SCV002236291.3

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This missense change has been observed in individual(s) with Wilson disease (PMID: 22763723). This sequence change replaces arginine with serine at codon 816 of the ATP7B protein (p.Arg816Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine.

#	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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