NM_170665.4(ATP2A2):c.2104G>A (p.Asp702Asn) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 12, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003557787.4

Allele description [Variation Report for NM_170665.4(ATP2A2):c.2104G>A (p.Asp702Asn)]

NM_170665.4(ATP2A2):c.2104G>A (p.Asp702Asn)

Gene:

ATP2A2:ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.11

Genomic location:

Preferred name:

NM_170665.4(ATP2A2):c.2104G>A (p.Asp702Asn)

HGVS:

NC_000012.12:g.110342234G>A
NG_007097.2:g.65608G>A
NM_001413013.1:c.1999G>A
NM_001413014.1:c.2104G>A
NM_001413015.1:c.1729G>A
NM_001681.4:c.2104G>A
NM_170665.4:c.2104G>AMANE SELECT
NP_001399942.1:p.Asp667Asn
NP_001399943.1:p.Asp702Asn
NP_001399944.1:p.Asp577Asn
NP_001672.1:p.Asp702Asn
NP_733765.1:p.Asp702Asn
NC_000012.11:g.110780039G>A
NM_170665.3:c.2104G>A

Protein change:

D577N

Links:

dbSNP: rs2548563282

NCBI 1000 Genomes Browser:

rs2548563282

Molecular consequence:

NM_001413013.1:c.1999G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001413014.1:c.2104G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001413015.1:c.1729G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001681.4:c.2104G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170665.4:c.2104G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004296226	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10441323, 15186327, 19528419, 12975374, 16766529, 28492532
SCV006088090	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 12, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004296226

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 17, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV006088090

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 12, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of novel ATP2A2 mutations in patients with Darier's disease.

Sakuntabhai A, Burge S, Monk S, Hovnanian A.

Hum Mol Genet. 1999 Sep;8(9):1611-9.

PubMed [citation]

PMID:: 10441323

Identification of mutations in the ATP2A2 gene in patients with Darier's disease from Hungary.

Rácz E, Csikós M, Kornsée Z, Horváth A, Kárpáti S.

Exp Dermatol. 2004 Jun;13(6):396-9.

PubMed [citation]

PMID:: 15186327

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296226.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 702 of the ATP2A2 protein (p.Asp702Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Darier disease (PMID: 10441323, 15186327, 19528419; Invitae). 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 expected to disrupt ATP2A2 protein function. Experimental studies have shown that this missense change affects ATP2A2 function (PMID: 12975374, 16766529). 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 GeneDx, SCV006088090.1

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

Description

Published functional studies demonstrate severe loss of enzyme activity and impaired protein function (PMID: 12975374); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 12072062, 23356892, 28035777, 26471493, 15186327, 19528419, 30345710, 1831454, 16766529, 12975374, 10441323)

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

Last Updated: Jun 29, 2025

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