dbSNP rs241509: ATP2B2:c.2703+9G>T (chr3-10345375-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001001331.4(ATP2B2):c.2703+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,613,588 control chromosomes in the GnomAD database, including 156,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11630 hom., cov: 33)

Exomes 𝑓: 0.44 ( 145252 hom. )

Consequence

ATP2B2
NM_001001331.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.497

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 3-10345375-C-A is Benign according to our data. Variant chr3-10345375-C-A is described in ClinVar as [Benign]. Clinvar id is 1247918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4 link	c.2703+9G>T		intron_variant	Intron 18 of 22	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.2703+9G>T		intron_variant	Intron 18 of 22	5	NM_001001331.4	ENSP00000353414.2		Q01814-1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55629

AN:

152018

Hom.:

11635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.517

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.547

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.390

GnomAD3 exomes

AF:

0.451

AC:

112944

AN:

250682

Hom.:

27112

AF XY:

0.455

AC XY:

61729

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.593

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.507

Gnomad SAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.441

AC:

643989

AN:

1461450

Hom.:

145252

Cov.:

AF XY:

0.444

AC XY:

322761

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.582

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.561

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.366

AC:

55633

AN:

152138

Hom.:

11630

Cov.:

AF XY:

0.373

AC XY:

27764

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.508

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.546

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.386

Alfa

AF:

0.392

Hom.:

6101

Bravo

AF:

0.358

EpiCase

AF:

0.423

EpiControl

AF:

0.420

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

- -

Nov 29, 2019

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.4

DANN

Benign

0.78

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