NM_000052.7(ATP7A):c.1933C>T (p.Arg645Ter) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 11, 2024
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:: RCV001271473.7

Allele description [Variation Report for NM_000052.7(ATP7A):c.1933C>T (p.Arg645Ter)]

NM_000052.7(ATP7A):c.1933C>T (p.Arg645Ter)

Gene:

ATP7A:ATPase copper transporting alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq21.1

Genomic location:

Preferred name:

NM_000052.7(ATP7A):c.1933C>T (p.Arg645Ter)

HGVS:

NC_000023.11:g.78011239C>T
NG_013224.2:g.105543C>T
NM_000052.7:c.1933C>TMANE SELECT
NM_001282224.2:c.1933C>T
NP_000043.4:p.Arg645Ter
NP_001269153.1:p.Arg645Ter
NP_001269153.1:p.Arg645Ter
NC_000023.10:g.77266736C>T
NM_000052.4:c.1933C>T
NM_000052.6:c.1933C>T
NM_001282224.1:c.1933C>T
p.Arg645*

Protein change:

R645*

Links:

dbSNP: rs72554640

NCBI 1000 Genomes Browser:

rs72554640

Molecular consequence:

NM_000052.7:c.1933C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282224.2:c.1933C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Menkes kinky-hair syndrome (MNK)
Synonyms:: Kinky hair disease; Copper transport disease; Menkes Disease
Identifiers:: MONDO: MONDO:0010651; MedGen: C0022716; Orphanet: 565; OMIM: 309400

Name:: Cutis laxa, X-linked (OHS)
Synonyms:: EDS IX; Occipital horn syndrome; Ehlers-Danlos syndrome, occipital horn type (formerly); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010572; MedGen: C0268353; Orphanet: 198; OMIM: 304150

Name:: X-linked distal spinal muscular atrophy type 3
Synonyms:: SPINAL MUSCULAR ATROPHY, DISTAL, X-LINKED RECESSIVE; NEURONOPATHY, DISTAL HEREDITARY MOTOR, X-LINKED; NEUROPATHY, DISTAL HEREDITARY MOTOR, X-LINKED
Identifiers:: MONDO: MONDO:0010338; MedGen: C1845359; Orphanet: 139557; OMIM: 300489

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001452640	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV002238921	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11241493, 20652413, 7977350, 32005694, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001452640

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 16, 2020)

germline

clinical testing

SCV002238921

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2024)

germline

clinical testing

PubMed (5)
[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

ATP7A gene mutations in 16 patients with Menkes disease and a patient with occipital horn syndrome.

Gu YH, Kodama H, Murata Y, Mochizuki D, Yanagawa Y, Ushijima H, Shiba T, Lee CC.

Am J Med Genet. 2001 Mar 15;99(3):217-22.

PubMed [citation]

PMID:: 11241493

Molecular correlates of epilepsy in early diagnosed and treated Menkes disease.

Kaler SG, Liew CJ, Donsante A, Hicks JD, Sato S, Greenfield JC.

J Inherit Metab Dis. 2010 Oct;33(5):583-9. doi: 10.1007/s10545-010-9118-2. Epub 2010 Jul 21.

PubMed [citation]

PMID:: 20652413
PMCID:: PMC3113468

See all PubMed Citations (5)

Details of each submission

From Natera, Inc., SCV001452640.1

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

#	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 Invitae, SCV002238921.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg645*) in the ATP7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7A are known to be pathogenic (PMID: 11241493, 20652413). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ATP7A-related conditions (PMID: 7977350, 32005694). ClinVar contains an entry for this variant (Variation ID: 210404). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

Last Updated: Mar 5, 2024

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