NM_000053.4(ATP7B):c.2251G>T (p.Ala751Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 15, 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:: RCV003155276.1

Allele description [Variation Report for NM_000053.4(ATP7B):c.2251G>T (p.Ala751Ser)]

NM_000053.4(ATP7B):c.2251G>T (p.Ala751Ser)

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.2251G>T (p.Ala751Ser)

HGVS:

NC_000013.11:g.51958415C>A
NG_008806.1:g.58080G>T
NM_000053.4:c.2251G>TMANE SELECT
NM_001005918.3:c.1870-808G>T
NM_001243182.2:c.1918G>T
NM_001330578.2:c.2122-808G>T
NM_001330579.2:c.1999G>T
NP_000044.2:p.Ala751Ser
NP_001230111.1:p.Ala640Ser
NP_001317508.1:p.Ala667Ser
NC_000013.10:g.52532551C>A
NM_000053.3:c.2251G>T

Protein change:

A640S

Links:

dbSNP: rs1555291181

NCBI 1000 Genomes Browser:

rs1555291181

Molecular consequence:

NM_001005918.3:c.1870-808G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001330578.2:c.2122-808G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000053.4:c.2251G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243182.2:c.1918G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330579.2:c.1999G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844740	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27022412, 34470610 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844740

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis.

Dong Y, Ni W, Chen WJ, Wan B, Zhao GX, Shi ZQ, Zhang Y, Wang N, Yu L, Xu JF, Wu ZY.

Theranostics. 2016;6(5):638-49. doi: 10.7150/thno.14596.

PubMed [citation]

PMID:: 27022412
PMCID:: PMC4805659

Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease.

Li M, Ma J, Wang W, Yang X, Luo K.

BMC Gastroenterol. 2021 Sep 1;21(1):339. doi: 10.1186/s12876-021-01911-5.

PubMed [citation]

PMID:: 34470610
PMCID:: PMC8411542

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844740.1

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

Description

Variant summary: ATP7B c.2251G>T (p.Ala751Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249584 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2251G>T has been reported in the literature in individuals affected with Wilson Disease with non informative genotypes (example:Dong_2016 and Li_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Wilson Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: Apr 1, 2023

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