chr3-10328802-G-C

Variant names:

• chr3-10328802-G-C
• rs4327369
• NM_001001331.4:c.*12C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001331.4(ATP2B2):​c.*12C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,596,812 control chromosomes in the GnomAD database, including 75,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9507 hom., cov: 29)
  • Exomes 𝑓: 0.29 (65569 hom.)
• Consequence: ATP2B2 NM_001001331.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.256
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 3-10328802-G-C is Benign according to our data. Variant chr3-10328802-G-C is described in ClinVar as Benign. ClinVar VariationId is 1279072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 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.*12C>G		3_prime_UTR	Exon 23 of 23	NP_001001331.1	Q01814-1
	ATP2B2	NM_001438646.1		c.*12C>G		3_prime_UTR	Exon 21 of 21	NP_001425575.1
	ATP2B2	NM_001353564.1		c.*12C>G		3_prime_UTR	Exon 21 of 21	NP_001340493.1	Q01814-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B2	ENST00000360273.7	TSL:5 MANE Select	c.*12C>G		3_prime_UTR	Exon 23 of 23	ENSP00000353414.2	Q01814-1
	ATP2B2	ENST00000452124.2	TSL:1	c.*12C>G		3_prime_UTR	Exon 20 of 20	ENSP00000414854.2	Q01814-8
	ATP2B2	ENST00000397077.6	TSL:1	c.*12C>G		3_prime_UTR	Exon 20 of 20	ENSP00000380267.1	Q01814-6

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51074 AN: 151356 Hom.: 9493 Cov.: 29

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.344 AC: 84436 AN: 245646 AF XY: 0.343

Gnomad AFR exome AF: 0.445

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.590

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.287 AC: 414710 AN: 1445338 Hom.: 65569 Cov.: 35 AF XY: 0.291 AC XY: 208362 AN XY: 715790

African (AFR) AF: 0.449 AC: 14868 AN: 33146

American (AMR) AF: 0.386 AC: 17055 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6225 AN: 25592

East Asian (EAS) AF: 0.624 AC: 24519 AN: 39322

South Asian (SAS) AF: 0.469 AC: 39723 AN: 84674

European-Finnish (FIN) AF: 0.344 AC: 18214 AN: 52916

Middle Eastern (MID) AF: 0.277 AC: 1576 AN: 5698

European-Non Finnish (NFE) AF: 0.250 AC: 274575 AN: 1100090

Other (OTH) AF: 0.301 AC: 17955 AN: 59684

GnomAD4 genome AF: 0.338 AC: 51139 AN: 151474 Hom.: 9507 Cov.: 29 AF XY: 0.346 AC XY: 25611 AN XY: 73994

African (AFR) AF: 0.442 AC: 18205 AN: 41204

American (AMR) AF: 0.337 AC: 5134 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3466

East Asian (EAS) AF: 0.587 AC: 2997 AN: 5108

South Asian (SAS) AF: 0.496 AC: 2368 AN: 4778

European-Finnish (FIN) AF: 0.336 AC: 3527 AN: 10512

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17028 AN: 67894

Other (OTH) AF: 0.311 AC: 652 AN: 2094

Alfa AF: 0.290 Hom.: 1305

Bravo AF: 0.343

Asia WGS AF: 0.527 AC: 1828 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.9
DANN	Benign	0.79
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

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: rs4327369; hg19: chr3-10370486; COSMIC: COSV59489676; COSMIC: COSV59489676;