chr3-10581257-A-C

Variant names:

• chr3-10581257-A-C
• rs6803992
• NM_001353564.1:c.-415+38660T>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.-415+38660T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,134 control chromosomes in the GnomAD database, including 22,514 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 0.53 (22514 hom., cov: 33)
• Consequence: ATP2B2 NM_001353564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal dominant 82

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353564.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	NM_001353564.1		c.-415+38660T>G		intron	N/A	NP_001340493.1	Q01814-6
	ATP2B2	NM_001438036.1		c.-415+38660T>G		intron	N/A	NP_001424965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	ENST00000646379.1		c.-415+38660T>G		intron	N/A	ENSP00000494381.1	Q01814-6

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81263 AN: 152016 Hom.: 22488 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.535 AC: 81344 AN: 152134 Hom.: 22514 Cov.: 33 AF XY: 0.541 AC XY: 40262 AN XY: 74360

African (AFR) AF: 0.617 AC: 25618 AN: 41508

American (AMR) AF: 0.515 AC: 7883 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3470

East Asian (EAS) AF: 0.860 AC: 4451 AN: 5174

South Asian (SAS) AF: 0.666 AC: 3215 AN: 4824

European-Finnish (FIN) AF: 0.517 AC: 5469 AN: 10570

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31795 AN: 67978

Other (OTH) AF: 0.519 AC: 1098 AN: 2114

Alfa AF: 0.479 Hom.: 31467

Bravo AF: 0.538

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		-0.58
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: rs6803992; hg19: chr3-10622941;