rs6807064

Variant names:

• chr3-10494087-C-T
• rs6807064
• NM_001001331.4:c.-320+11378G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001331.4(ATP2B2):​c.-320+11378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,938 control chromosomes in the GnomAD database, including 9,660 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 0.34 (9660 hom., cov: 32)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 17 publications found

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]

ATP2B2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 82

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive nonsyndromic hearing loss 12

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4	c.-320+11378G>A		intron_variant	Intron 1 of 22	ENST00000360273.7	NP_001001331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000360273.7	c.-320+11378G>A		intron_variant	Intron 1 of 22	5	NM_001001331.4	ENSP00000353414.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52153 AN: 151820 Hom.: 9651 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.344 AC: 52206 AN: 151938 Hom.: 9660 Cov.: 32 AF XY: 0.342 AC XY: 25431 AN XY: 74274

African (AFR) AF: 0.476 AC: 19729 AN: 41420

American (AMR) AF: 0.396 AC: 6052 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1075 AN: 5160

South Asian (SAS) AF: 0.301 AC: 1443 AN: 4800

European-Finnish (FIN) AF: 0.287 AC: 3034 AN: 10554

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18839 AN: 67954

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.300 Hom.: 29761

Bravo AF: 0.359

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.087
DANN	Benign	0.67
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6807064; hg19: chr3-10535771;