rs56243033

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_170665.4(ATP2A2):c.2172G>A(p.Ala724Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,614,176 control chromosomes in the GnomAD database, including 3,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 228 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3403 hom. )

Consequence

ATP2A2
NM_170665.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.888

Publications

22 publications found

Variant links:

Genes affected

ATP2A2 (HGNC:812): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

ATP2A2 Gene-Disease associations (from GenCC):

acrokeratosis verruciformis
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
Darier disease
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Illumina

ATP2A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.021).

BP6

Variant 12-110342302-G-A is Benign according to our data. Variant chr12-110342302-G-A is described in ClinVar as Benign. ClinVar VariationId is 307178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.888 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A2	NM_170665.4 link	c.2172G>A	p.Ala724Ala	synonymous_variant	Exon 15 of 20	ENST00000539276.7	NP_733765.1	P16615-1A0A0S2Z3L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A2	ENST00000539276.7 link	c.2172G>A	p.Ala724Ala	synonymous_variant	Exon 15 of 20	1	NM_170665.4	ENSP00000440045.2		P16615-1

Frequencies

GnomAD3 genomes

AF:

0.0467

AC:

7113

AN:

152170

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0482

Gnomad FIN

AF:

0.0752

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.0726

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0527

AC:

13260

AN:

251464

AF XY:

0.0551

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0230

Gnomad ASJ exome

AF:

0.0287

Gnomad EAS exome

AF:

0.000761

Gnomad FIN exome

AF:

0.0715

Gnomad NFE exome

AF:

0.0746

Gnomad OTH exome

AF:

0.0536

GnomAD4 exome

AF:

0.0652

AC:

95276

AN:

1461888

Hom.:

3403

Cov.:

AF XY:

0.0656

AC XY:

47721

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00944

AC:

316

AN:

33480

American (AMR)

AF:

0.0236

AC:

1057

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0312

AC:

815

AN:

26136

East Asian (EAS)

AF:

0.000353

AC:

AN:

39700

South Asian (SAS)

AF:

0.0546

AC:

4709

AN:

86258

European-Finnish (FIN)

AF:

0.0747

AC:

3991

AN:

53420

Middle Eastern (MID)

AF:

0.0479

AC:

276

AN:

5768

European-Non Finnish (NFE)

AF:

0.0726

AC:

80762

AN:

1112006

Other (OTH)

AF:

0.0552

AC:

3336

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

6053

12107

18160

24214

30267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2864

5728

8592

11456

14320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0467

AC:

7115

AN:

152288

Hom.:

228

Cov.:

AF XY:

0.0446

AC XY:

3323

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0114

AC:

475

AN:

41562

American (AMR)

AF:

0.0275

AC:

420

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0484

AC:

234

AN:

4832

European-Finnish (FIN)

AF:

0.0752

AC:

798

AN:

10616

Middle Eastern (MID)

AF:

0.0514

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0727

AC:

4943

AN:

68018

Other (OTH)

AF:

0.0327

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

368

736

1103

1471

1839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0503

Hom.:

205

Bravo

AF:

0.0405

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0663

EpiControl

AF:

0.0658

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17439322, 20687374) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Keratosis follicularis

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Acrokeratosis verruciformis of Hopf

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.56

(source)

DANN

Benign

0.46

PhyloP100

-0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over