rs12632101

Variant names:

• chr3-10575794-T-C
• rs12632101
• NM_001353564.1:c.-414-41661A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-10575794-T-C
• chr3-10575794-T-G

Variant summary

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

The NM_001353564.1(ATP2B2):​c.-414-41661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,048 control chromosomes in the GnomAD database, including 7,716 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 0.31 (7716 hom., cov: 32)
• Consequence: ATP2B2 NM_001353564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001353564.1	c.-414-41661A>G		intron_variant	Intron 1 of 20		NP_001340493.1
ATP2B2	NM_001438036.1	c.-414-41661A>G		intron_variant	Intron 2 of 21		NP_001424965.1
ATP2B2	XM_005265179.6	c.-414-41661A>G		intron_variant	Intron 2 of 24		XP_005265236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000646379.1	c.-414-41661A>G		intron_variant	Intron 2 of 21			ENSP00000494381.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46729 AN: 151930 Hom.: 7683 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.308 AC: 46817 AN: 152048 Hom.: 7716 Cov.: 32 AF XY: 0.313 AC XY: 23270 AN XY: 74306

African (AFR) AF: 0.388 AC: 16088 AN: 41448

American (AMR) AF: 0.304 AC: 4653 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2572 AN: 5174

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4814

European-Finnish (FIN) AF: 0.327 AC: 3462 AN: 10576

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16804 AN: 67972

Other (OTH) AF: 0.275 AC: 579 AN: 2104

Alfa AF: 0.266 Hom.: 3544

Bravo AF: 0.310

Asia WGS AF: 0.460 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.83
DANN	Benign	0.80
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12632101; hg19: chr3-10617478;