NM_000053.4(ATP7B):c.3852_3875del (p.Gly1285_Ile1292del) AND Wilson disease

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jul 9, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000671069.9

Allele description [Variation Report for NM_000053.4(ATP7B):c.3852_3875del (p.Gly1285_Ile1292del)]

NM_000053.4(ATP7B):c.3852_3875del (p.Gly1285_Ile1292del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q14.3

Genomic location:

Preferred name:

NM_000053.4(ATP7B):c.3852_3875del (p.Gly1285_Ile1292del)

HGVS:

NC_000013.11:g.51937513_51937536del
NG_008806.1:g.78968_78991del
NM_000053.4:c.3852_3875delMANE SELECT
NM_001005918.3:c.3231_3254del
NM_001243182.2:c.3519_3542del
NM_001330578.2:c.3618_3641del
NM_001330579.2:c.3600_3623del
NP_000044.2:p.Gly1285_Ile1292del
NP_001005918.1:p.Gly1078_Ile1085del
NP_001230111.1:p.Gly1174_Ile1181del
NP_001317507.1:p.Gly1207_Ile1214del
NP_001317508.1:p.Gly1201_Ile1208del
NC_000013.10:g.52511640_52511663del
NC_000013.10:g.52511649_52511672del
NM_000053.3:c.3852_3875del24

Links:

dbSNP: rs1555283826

NCBI 1000 Genomes Browser:

rs1555283826

Molecular consequence:

NM_000053.4:c.3852_3875del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001005918.3:c.3231_3254del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001243182.2:c.3519_3542del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001330578.2:c.3618_3641del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001330579.2:c.3600_3623del - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV000796010	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Nov 27, 2017)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9222767, 8533760 Citation Link,
SCV001505364	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 9, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9222767, 16416207, 17410460, 28492532
SCV002027148	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 5, 2021)	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

SCV000796010

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Nov 27, 2017)

unknown

clinical testing

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

Citation Link,

SCV001505364

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 9, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002027148

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 5, 2021)

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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.

Figus A, Angius A, Loudianos G, Bertini C, Dessi V, Loi A, Deiana M, Lovicu M, Olla N, Sole G, et al.

Am J Hum Genet. 1995 Dec;57(6):1318-24.

PubMed [citation]

PMID:: 8533760
PMCID:: PMC1801406

24 bp deletion and Ala1278 to Val mutation of the ATP7B gene in a Sardinian family with Wilson disease.

Orrù S, Thomas G, Loizedda A, Cox DW, Contu L.

Hum Mutat. 1997;10(1):84-5. No abstract available.

PubMed [citation]

PMID:: 9222767

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000796010.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001505364.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant, c.3852_3875del, results in the deletion of 8 amino acid(s) of the ATP7B protein (p.Gly1285_Ile1292del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Wilson's disease (PMID: 9222767). ClinVar contains an entry for this variant (Variation ID: 555278). This variant disrupts a region of the ATP7B protein in which other variant(s) (p.Thr1288Arg) have been determined to be pathogenic (PMID: 16416207, 17410460). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as 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

From Genome-Nilou Lab, SCV002027148.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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