3-10466811-T-C

Variant names:

• chr3-10466811-T-C
• rs34872
• NM_001001331.4:c.-319-16949A>G

Variant summary

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

The NM_001001331.4(ATP2B2):​c.-319-16949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,154 control chromosomes in the GnomAD database, including 27,866 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 0.60 (27866 hom., cov: 33)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4	c.-319-16949A>G		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.-319-16949A>G		intron_variant	Intron 1 of 22	5	NM_001001331.4	ENSP00000353414.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90788 AN: 152036 Hom.: 27845 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.597 AC: 90852 AN: 152154 Hom.: 27866 Cov.: 33 AF XY: 0.602 AC XY: 44778 AN XY: 74392

African (AFR) AF: 0.725 AC: 30077 AN: 41490

American (AMR) AF: 0.580 AC: 8866 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3470

East Asian (EAS) AF: 0.730 AC: 3786 AN: 5186

South Asian (SAS) AF: 0.698 AC: 3367 AN: 4824

European-Finnish (FIN) AF: 0.558 AC: 5906 AN: 10582

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34863 AN: 67988

Other (OTH) AF: 0.588 AC: 1242 AN: 2114

Alfa AF: 0.543 Hom.: 50330

Bravo AF: 0.600

Asia WGS AF: 0.725 AC: 2522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		-0.093
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: rs34872; hg19: chr3-10508495;