3-10548262-C-T

Position:

• chr3-10548262-C-T

Variant summary

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

The NM_001353564.1(ATP2B2):​c.-414-14129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,302 control chromosomes in the GnomAD database, including 365 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 0.050 (365 hom., cov: 32)
• Consequence: ATP2B2 NM_001353564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2B2	NM_001353564.1	c.-414-14129G>A		intron_variant			NP_001340493.1
ATP2B2	XM_005265179.6	c.-414-14129G>A		intron_variant			XP_005265236.1
ATP2B2	XM_006713175.5	c.-414-14129G>A		intron_variant			XP_006713238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000646379.1	c.-414-14129G>A		intron_variant				ENSP00000494381.1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7666 AN: 152184 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0504 AC: 7672 AN: 152302 Hom.: 365 Cov.: 32 AF XY: 0.0511 AC XY: 3807 AN XY: 74468

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0828

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0554 Hom.: 62

Bravo AF: 0.0521

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17033062; hg19: chr3-10589946;