rs6442177

Positions:

• chr3-10532283-A-G
• chr3-10532283-A-T

Variant summary

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

The NM_001353564.1(ATP2B2):​c.-320+1756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,074 control chromosomes in the GnomAD database, including 10,428 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 0.37 (10428 hom., cov: 32)
• Consequence: ATP2B2 NM_001353564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2B2	NM_001353564.1	c.-320+1756T>C		intron_variant			NP_001340493.1
ATP2B2	XM_005265179.6	c.-320+1756T>C		intron_variant			XP_005265236.1
ATP2B2	XM_006713175.5	c.-320+1756T>C		intron_variant			XP_006713238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000646379.1	c.-320+1756T>C		intron_variant				ENSP00000494381	A1
ATP2B2	ENST00000460129.5	c.-320+1756T>C		intron_variant, NMD_transcript_variant		5		ENSP00000424494

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55531 AN: 151956 Hom.: 10422 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.365 AC: 55562 AN: 152074 Hom.: 10428 Cov.: 32 AF XY: 0.368 AC XY: 27351 AN XY: 74332

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.371

Alfa AF: 0.387 Hom.: 23987

Bravo AF: 0.352

Asia WGS AF: 0.325 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6442177; hg19: chr3-10573967;