chr3-10666176-G-A

Variant names:

• chr3-10666176-G-A
• rs892605
• NM_001438036.1:c.-460+41739C>T

Variant summary

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

The NM_001438036.1(ATP2B2):​c.-460+41739C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,052 control chromosomes in the GnomAD database, including 45,635 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 0.77 (45635 hom., cov: 31)
• Consequence: ATP2B2 NM_001438036.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001438036.1	c.-460+41739C>T		intron_variant	Intron 1 of 21		NP_001424965.1
ATP2B2	XM_005265179.6	c.-460+25215C>T		intron_variant	Intron 1 of 24		XP_005265236.1
ATP2B2	XM_006713175.5	c.-460+41739C>T		intron_variant	Intron 1 of 24		XP_006713238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000646379.1	c.-460+41739C>T		intron_variant	Intron 1 of 21			ENSP00000494381.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117136 AN: 151934 Hom.: 45594 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.771 AC: 117231 AN: 152052 Hom.: 45635 Cov.: 31 AF XY: 0.770 AC XY: 57258 AN XY: 74320

African (AFR) AF: 0.890 AC: 36918 AN: 41496

American (AMR) AF: 0.781 AC: 11941 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2184 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3798 AN: 5148

South Asian (SAS) AF: 0.733 AC: 3529 AN: 4812

European-Finnish (FIN) AF: 0.729 AC: 7707 AN: 10574

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48801 AN: 67958

Other (OTH) AF: 0.753 AC: 1586 AN: 2106

Alfa AF: 0.739 Hom.: 71913

Bravo AF: 0.780

Asia WGS AF: 0.763 AC: 2653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		-0.12
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: rs892605; hg19: chr3-10707861;