Variant 3-10338239-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001001331.4(ATP2B2):c.3357G>A(p.Ala1119=) 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:2

Conservation

PhyloP100: -3.53

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
ATP2B2	NM_001001331.4 linkuse as main transcript	c.3357G>A	p.Ala1119=	synonymous_variant	22/23	ENST00000360273.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B2	ENST00000360273.7 linkuse as main transcript	c.3357G>A	p.Ala1119=	synonymous_variant	22/23	5	NM_001001331.4		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

GnomAD3 exomes

AF:

0.491

AC:

123399

AN:

251364

Hom.:

32223

AF XY:

0.488

AC XY:

66252

AN XY:

135864

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 SAS exome

AF:

0.620

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

Gnomad4 AFR exome

AF:

0.552

Gnomad4 AMR exome

AF:

0.677

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.402

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.477

AC:

72536

AN:

152102

Hom.:

17883

Cov.:

AF XY:

0.482

AC XY:

35852

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.547

Gnomad4 AMR

AF:

0.581

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.554

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.432

Hom.:

6770

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.035

DANN

Benign

0.94

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.27

MetaRNN

Benign

0.000034

MutationTaster

Benign

6.1e-14

P;P;P;P;P

GERP RS

-9.2

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over