3-10337939-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001001331.4(ATP2B2):c.3420+237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,020 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.068 (517 hom., cov: 33)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-10337939-A-G is Benign according to our data. Variant chr3-10337939-A-G is described in ClinVar as [Benign]. Clinvar id is 1262156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B2	NM_001001331.4	c.3420+237T>C		intron_variant		ENST00000360273.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B2	ENST00000360273.7	c.3420+237T>C		intron_variant		5	NM_001001331.4

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10340 AN: 151902 Hom.: 518 Cov.: 33

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0680 AC: 10339 AN: 152020 Hom.: 517 Cov.: 33 AF XY: 0.0701 AC XY: 5207 AN XY: 74318

Gnomad4 AFR AF: 0.0488

Gnomad4 AMR AF: 0.0698

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0656 Hom.: 73

Bravo AF: 0.0682

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.18
Dann	Benign	0.33

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

Other links and lift over

dbSNP: rs4684040; hg19: chr3-10379623;