3-10337919-T-C

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+257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,034 control chromosomes in the GnomAD database, including 18,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18654 hom., cov: 33)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23

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=-0.93).
• BP6: Variant 3-10337919-T-C is Benign according to our data. Variant chr3-10337919-T-C is described in ClinVar as [Benign]. Clinvar id is 1277323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B2	NM_001001331.4	c.3420+257A>G		intron_variant		ENST00000360273.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B2	ENST00000360273.7	c.3420+257A>G		intron_variant		5	NM_001001331.4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74276 AN: 151914 Hom.: 18632 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.489 AC: 74335 AN: 152034 Hom.: 18654 Cov.: 33 AF XY: 0.492 AC XY: 36584 AN XY: 74316

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.484

Alfa AF: 0.487 Hom.: 2306

Bravo AF: 0.498

Asia WGS AF: 0.570 AC: 1986 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.20
Dann	Benign	0.35

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: rs40336; hg19: chr3-10379603;