rs12632101

Positions:

• chr3-10575794-T-C
• chr3-10575794-T-G

Variant summary

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

The NM_001353564.1(ATP2B2):​c.-414-41661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,048 control chromosomes in the GnomAD database, including 7,716 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 0.31 (7716 hom., cov: 32)
• Consequence: ATP2B2 NM_001353564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B2	NM_001353564.1	c.-414-41661A>G		intron_variant
ATP2B2	XM_005265179.6	c.-414-41661A>G		intron_variant
ATP2B2	XM_006713175.5	c.-414-41661A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B2	ENST00000646379.1	c.-414-41661A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46729 AN: 151930 Hom.: 7683 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.308 AC: 46817 AN: 152048 Hom.: 7716 Cov.: 32 AF XY: 0.313 AC XY: 23270 AN XY: 74306

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.275

Alfa AF: 0.267 Hom.: 3302

Bravo AF: 0.310

Asia WGS AF: 0.460 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.83
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12632101; hg19: chr3-10617478;