rs749477

Variant names:

• chr3-10615138-G-A
• rs749477
• NM_001353564.1:c.-415+4779C>T

Variant summary

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

The NM_001353564.1(ATP2B2):​c.-415+4779C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,922 control chromosomes in the GnomAD database, including 21,735 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 0.52 (21735 hom., cov: 31)
• Consequence: ATP2B2 NM_001353564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001353564.1	c.-415+4779C>T		intron_variant	Intron 1 of 20		NP_001340493.1
ATP2B2	NM_001438036.1	c.-415+4779C>T		intron_variant	Intron 2 of 21		NP_001424965.1
ATP2B2	XM_005265179.6	c.-415+4779C>T		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.-415+4779C>T		intron_variant	Intron 2 of 21			ENSP00000494381.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79612 AN: 151802 Hom.: 21726 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.524 AC: 79656 AN: 151922 Hom.: 21735 Cov.: 31 AF XY: 0.522 AC XY: 38755 AN XY: 74288

African (AFR) AF: 0.443 AC: 18331 AN: 41412

American (AMR) AF: 0.554 AC: 8463 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2106 AN: 3468

East Asian (EAS) AF: 0.138 AC: 710 AN: 5158

South Asian (SAS) AF: 0.375 AC: 1802 AN: 4800

European-Finnish (FIN) AF: 0.610 AC: 6444 AN: 10558

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39760 AN: 67938

Other (OTH) AF: 0.547 AC: 1155 AN: 2110

Alfa AF: 0.563 Hom.: 64780

Bravo AF: 0.518

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.80
PhyloP100		-0.069
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: rs749477; hg19: chr3-10656823;