rs2289274

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4 link	c.1437C>T	p.Asn479Asn	synonymous_variant	Exon 12 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.1437C>T	p.Asn479Asn	synonymous_variant	Exon 12 of 23	5	NM_001001331.4	ENSP00000353414.2		Q01814-1

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

GnomAD3 exomes

AF:

0.308

AC:

77453

AN:

251400

Hom.:

12305

AF XY:

0.312

AC XY:

42435

AN XY:

135872

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 SAS exome

AF:

0.360

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

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.299

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.272

AC:

41342

AN:

152128

Hom.:

6052

Cov.:

AF XY:

0.274

AC XY:

20392

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.346

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.296

Hom.:

8436

Bravo

AF:

0.267

Asia WGS

AF:

0.295

AC:

1028

AN:

3478

EpiCase

AF:

0.303

EpiControl

AF:

0.305

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 10, 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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Associated with severe COVID-19 disease

Pathogenic:1

Jul 01, 2023

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: Likely risk allele

Review Status: no assertion criteria provided

Collection Method: research

The allele G is a risk for non-surviving in patients with severe COVID-19 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.3

DANN

Benign

0.70

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