rs6807064

chr3-10494087-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001331.4(ATP2B2):c.-320+11378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,938 control chromosomes in the GnomAD database, including 9,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9660 hom., cov: 32)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B2	NM_001001331.4	c.-320+11378G>A		intron_variant		ENST00000360273.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B2	ENST00000360273.7	c.-320+11378G>A		intron_variant		5	NM_001001331.4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52153 AN: 151820 Hom.: 9651 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.344 AC: 52206 AN: 151938 Hom.: 9660 Cov.: 32 AF XY: 0.342 AC XY: 25431 AN XY: 74274

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.328

Alfa AF: 0.292 Hom.: 14414

Bravo AF: 0.359

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.087
Dann	Benign	0.67

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: rs6807064; hg19: chr3-10535771;