rs2278556

Variant names:

• chr3-10360419-G-A
• rs2278556
• NM_001001331.4:c.1660-296C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-10360419-G-A
• chr3-10360419-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001001331.4(ATP2B2):​c.1660-296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,144 control chromosomes in the GnomAD database, including 10,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (10243 hom., cov: 33)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.720
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-10360419-G-A is Benign according to our data. Variant chr3-10360419-G-A is described in ClinVar as Benign. ClinVar VariationId is 1296800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	NM_001001331.4	MANE Select	c.1660-296C>T		intron	N/A	NP_001001331.1
	ATP2B2	NM_001438646.1		c.1567-296C>T		intron	N/A	NP_001425575.1
	ATP2B2	NM_001353564.1		c.1525-296C>T		intron	N/A	NP_001340493.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	ENST00000360273.7	TSL:5 MANE Select	c.1660-296C>T		intron	N/A	ENSP00000353414.2
	ATP2B2	ENST00000452124.2	TSL:1	c.1567-296C>T		intron	N/A	ENSP00000414854.2
	ATP2B2	ENST00000397077.6	TSL:1	c.1525-296C>T		intron	N/A	ENSP00000380267.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52788 AN: 152026 Hom.: 10244 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.347 AC: 52817 AN: 152144 Hom.: 10243 Cov.: 33 AF XY: 0.354 AC XY: 26361 AN XY: 74376

African (AFR) AF: 0.180 AC: 7459 AN: 41496

American (AMR) AF: 0.495 AC: 7573 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2818 AN: 5184

South Asian (SAS) AF: 0.521 AC: 2516 AN: 4830

European-Finnish (FIN) AF: 0.394 AC: 4165 AN: 10578

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25898 AN: 67974

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.372 Hom.: 46020

Bravo AF: 0.343

Asia WGS AF: 0.534 AC: 1855 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		0.72
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: rs2278556; hg19: chr3-10402103;