rs9826066

chr3-10449546-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001331.4(ATP2B2):c.-3A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,614,214 control chromosomes in the GnomAD database, including 1,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (768 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (725 hom.)
• Consequence: ATP2B2 NM_001001331.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.103

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-10449546-T-C is Benign according to our data. Variant chr3-10449546-T-C is described in ClinVar as [Benign]. Clinvar id is 585335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B2	NM_001001331.4	c.-3A>G		5_prime_UTR_variant	2/23	ENST00000360273.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B2	ENST00000360273.7	c.-3A>G		5_prime_UTR_variant	2/23	5	NM_001001331.4

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8380 AN: 152220 Hom.: 763 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.0406

GnomAD3 exomes AF: 0.0153 AC: 3860 AN: 251478 Hom.: 308 AF XY: 0.0114 AC XY: 1549 AN XY: 135910

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00168

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.00687 AC: 10039 AN: 1461876 Hom.: 725 Cov.: 31 AF XY: 0.00610 AC XY: 4437 AN XY: 727238

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.000487

Gnomad4 NFE exome AF: 0.00133

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.0551 AC: 8399 AN: 152338 Hom.: 768 Cov.: 33 AF XY: 0.0534 AC XY: 3976 AN XY: 74500

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0318 Hom.: 215

Bravo AF: 0.0629

Asia WGS AF: 0.00924 AC: 33 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.5
Dann	Benign	0.82

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: rs9826066; hg19: chr3-10491230;