3-10338239-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001001331.4(ATP2B2):c.3357G>A(p.Ala1119Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,613,952 control chromosomes in the GnomAD database, including 166,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17883 hom., cov: 33)

Exomes 𝑓: 0.44 ( 148137 hom. )

Consequence

ATP2B2
NM_001001331.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.53

Publications

25 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3600707E-5).

BP6

Variant 3-10338239-C-T is Benign according to our data. Variant chr3-10338239-C-T is described in ClinVar as Benign. ClinVar VariationId is 1273978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4 link	c.3357G>A	p.Ala1119Ala	synonymous_variant	Exon 22 of 23	ENST00000360273.7	NP_001001331.1	Q01814-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000360273.7 link	c.3357G>A	p.Ala1119Ala	synonymous_variant	Exon 22 of 23	5	NM_001001331.4	ENSP00000353414.2		Q01814-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72478

AN:

151986

Hom.:

17869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.463

GnomAD2 exomes

AF:

0.491

AC:

123399

AN:

251364

AF XY:

0.488

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.689

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.452

GnomAD4 exome

AF:

0.443

AC:

648055

AN:

1461850

Hom.:

148137

Cov.:

AF XY:

0.447

AC XY:

325286

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.552

AC:

18482

AN:

33480

American (AMR)

AF:

0.677

AC:

30256

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

10048

AN:

26136

East Asian (EAS)

AF:

0.594

AC:

23591

AN:

39698

South Asian (SAS)

AF:

0.619

AC:

53400

AN:

86258

European-Finnish (FIN)

AF:

0.402

AC:

21449

AN:

53386

Middle Eastern (MID)

AF:

0.482

AC:

2779

AN:

5768

European-Non Finnish (NFE)

AF:

0.415

AC:

461204

AN:

1112004

Other (OTH)

AF:

0.445

AC:

26846

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

23147

46294

69441

92588

115735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14528

29056

43584

58112

72640

<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:

0.477

AC:

72536

AN:

152102

Hom.:

17883

Cov.:

AF XY:

0.482

AC XY:

35852

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.547

AC:

22715

AN:

41490

American (AMR)

AF:

0.581

AC:

8896

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1335

AN:

3472

East Asian (EAS)

AF:

0.554

AC:

2854

AN:

5150

South Asian (SAS)

AF:

0.619

AC:

2987

AN:

4822

European-Finnish (FIN)

AF:

0.390

AC:

4136

AN:

10602

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.413

AC:

28068

AN:

67956

Other (OTH)

AF:

0.460

AC:

970

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1904

3808

5711

7615

9519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.439

Hom.:

9493

Bravo

AF:

0.493

TwinsUK

AF:

0.415

AC:

1538

ALSPAC

AF:

0.424

AC:

1635

ESP6500AA

AF:

0.537

AC:

2365

ESP6500EA

AF:

0.415

AC:

3570

ExAC

AF:

0.486

AC:

59068

Asia WGS

AF:

0.578

AC:

2012

AN:

3478

EpiCase

AF:

0.417

EpiControl

AF:

0.408

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.035

(source)

DANN

Benign

0.94

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.27

MetaRNN

Benign

0.000034

PhyloP100

-3.5

GERP RS

-9.2

Mutation Taster

=100/0

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