dbSNP rs2289274: ATP2B2:p.Asn479Asn (chr3-10372031-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

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

The NM_001001331.4(ATP2B2):c.1437C>T(p.Asn479Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,946 control chromosomes in the GnomAD database, including 75,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6052 hom., cov: 32)

Exomes 𝑓: 0.31 ( 68980 hom. )

Consequence

ATP2B2
NM_001001331.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: 1.74

Publications

24 publications found

Variant links:

Genes affected

ATP2B2 (HGNC:815): (ATPase plasma membrane Ca2+ transporting 2) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 2. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ATP2B2 Gene-Disease associations (from GenCC):

hearing loss, autosomal dominant 82
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal recessive nonsyndromic hearing loss 12
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ATP2B2 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 (BayesDel_noAF=-0.46).

BP6

Variant 3-10372031-G-A is Benign according to our data. Variant chr3-10372031-G-A is described in ClinVar as Benign. ClinVar VariationId is 1291136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001331.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP2B2	NM_001001331.4	MANE Select	c.1437C>T	p.Asn479Asn	synonymous	Exon 12 of 23	NP_001001331.1
ATP2B2	NM_001438646.1		c.1344C>T	p.Asn448Asn	synonymous	Exon 10 of 21	NP_001425575.1
ATP2B2	NM_001353564.1		c.1302C>T	p.Asn434Asn	synonymous	Exon 10 of 21	NP_001340493.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATP2B2	ENST00000360273.7	TSL:5 MANE Select	c.1437C>T	p.Asn479Asn	synonymous	Exon 12 of 23	ENSP00000353414.2
ATP2B2	ENST00000452124.2	TSL:1	c.1344C>T	p.Asn448Asn	synonymous	Exon 9 of 20	ENSP00000414854.2
ATP2B2	ENST00000397077.6	TSL:1	c.1302C>T	p.Asn434Asn	synonymous	Exon 9 of 20	ENSP00000380267.1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41328

AN:

152010

Hom.:

6059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.308

AC:

77453

AN:

251400

AF XY:

0.312

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.312

Gnomad EAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.306

AC:

447228

AN:

1461818

Hom.:

68980

Cov.:

AF XY:

0.308

AC XY:

223847

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.160

AC:

5370

AN:

33480

American (AMR)

AF:

0.345

AC:

15417

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

8249

AN:

26136

East Asian (EAS)

AF:

0.299

AC:

11870

AN:

39698

South Asian (SAS)

AF:

0.356

AC:

30740

AN:

86254

European-Finnish (FIN)

AF:

0.294

AC:

15702

AN:

53408

Middle Eastern (MID)

AF:

0.287

AC:

1657

AN:

5766

European-Non Finnish (NFE)

AF:

0.306

AC:

339805

AN:

1111958

Other (OTH)

AF:

0.305

AC:

18418

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

19408

38816

58224

77632

97040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11214

22428

33642

44856

56070

<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:

0.272

AC:

41342

AN:

152128

Hom.:

6052

Cov.:

AF XY:

0.274

AC XY:

20392

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.163

AC:

6781

AN:

41504

American (AMR)

AF:

0.346

AC:

5284

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1087

AN:

3466

East Asian (EAS)

AF:

0.318

AC:

1647

AN:

5182

South Asian (SAS)

AF:

0.344

AC:

1653

AN:

4812

European-Finnish (FIN)

AF:

0.292

AC:

3089

AN:

10580

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20707

AN:

67986

Other (OTH)

AF:

0.277

AC:

586

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1524

3049

4573

6098

7622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.292

Hom.:

9798

Bravo

AF:

0.267

Asia WGS

AF:

0.295

AC:

1028

AN:

3478

EpiCase

AF:

0.303

EpiControl

AF:

0.305

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Associated with severe COVID-19 disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.3

(source)

DANN

Benign

0.70

PhyloP100

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over