3-10331156-T-C

Variant names:

• chr3-10331156-T-C
• rs26310
• NM_001001331.4:c.3421-2031A>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.3421-2031A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,098 control chromosomes in the GnomAD database, including 12,282 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 0.39 (12282 hom., cov: 33)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 5 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 = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001331.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	NM_001001331.4	MANE Select	c.3421-2031A>G		intron	N/A	NP_001001331.1
	ATP2B2	NM_001438646.1		c.3328-2031A>G		intron	N/A	NP_001425575.1
	ATP2B2	NM_001353564.1		c.3286-2031A>G		intron	N/A	NP_001340493.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	ENST00000360273.7	TSL:5 MANE Select	c.3421-2031A>G		intron	N/A	ENSP00000353414.2
	ATP2B2	ENST00000452124.2	TSL:1	c.3328-2031A>G		intron	N/A	ENSP00000414854.2
	ATP2B2	ENST00000397077.6	TSL:1	c.3286-2031A>G		intron	N/A	ENSP00000380267.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59599 AN: 151980 Hom.: 12275 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.392 AC: 59648 AN: 152098 Hom.: 12282 Cov.: 33 AF XY: 0.395 AC XY: 29396 AN XY: 74364

African (AFR) AF: 0.467 AC: 19382 AN: 41462

American (AMR) AF: 0.446 AC: 6816 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3466

East Asian (EAS) AF: 0.572 AC: 2957 AN: 5168

South Asian (SAS) AF: 0.419 AC: 2024 AN: 4828

European-Finnish (FIN) AF: 0.329 AC: 3486 AN: 10598

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22623 AN: 67970

Other (OTH) AF: 0.371 AC: 786 AN: 2116

Alfa AF: 0.352 Hom.: 16261

Bravo AF: 0.405

Asia WGS AF: 0.503 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.45
PhyloP100		0.51
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: rs26310; hg19: chr3-10372840;