3-10355304-T-C

Variant names:

• chr3-10355304-T-C
• rs3774180
• NM_001001331.4:c.2136+3387A>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.2136+3387A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,954 control chromosomes in the GnomAD database, including 11,172 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 0.37 (11172 hom., cov: 31)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4	c.2136+3387A>G		intron_variant	Intron 14 of 22	ENST00000360273.7	NP_001001331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000360273.7	c.2136+3387A>G		intron_variant	Intron 14 of 22	5	NM_001001331.4	ENSP00000353414.2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56518 AN: 151836 Hom.: 11171 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.372 AC: 56557 AN: 151954 Hom.: 11172 Cov.: 31 AF XY: 0.379 AC XY: 28185 AN XY: 74294

African (AFR) AF: 0.262 AC: 10834 AN: 41390

American (AMR) AF: 0.509 AC: 7777 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1066 AN: 3470

East Asian (EAS) AF: 0.519 AC: 2680 AN: 5160

South Asian (SAS) AF: 0.570 AC: 2749 AN: 4822

European-Finnish (FIN) AF: 0.381 AC: 4021 AN: 10566

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26024 AN: 67944

Other (OTH) AF: 0.386 AC: 816 AN: 2114

Alfa AF: 0.389 Hom.: 6088

Bravo AF: 0.371

Asia WGS AF: 0.574 AC: 1992 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		0.059
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: rs3774180; hg19: chr3-10396988;