3-10328802-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

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]

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4	c.*12C>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000360273.7	NP_001001331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000360273	c.*12C>G		3_prime_UTR_variant	Exon 23 of 23	5	NM_001001331.4	ENSP00000353414.2

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

Gnomad4 AFR exome AF: 0.449 AC: 14868 AN: 33146

Gnomad4 AMR exome AF: 0.386 AC: 17055 AN: 44216

Gnomad4 ASJ exome AF: 0.243 AC: 6225 AN: 25592

Gnomad4 EAS exome AF: 0.624 AC: 24519 AN: 39322

Gnomad4 SAS exome AF: 0.469 AC: 39723 AN: 84674

Gnomad4 FIN exome AF: 0.344 AC: 18214 AN: 52916

Gnomad4 NFE exome AF: 0.250 AC: 274575 AN: 1100090

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.442 AC: 0.441826 AN: 0.441826

Gnomad4 AMR AF: 0.337 AC: 0.337497 AN: 0.337497

Gnomad4 ASJ AF: 0.246 AC: 0.245817 AN: 0.245817

Gnomad4 EAS AF: 0.587 AC: 0.586727 AN: 0.586727

Gnomad4 SAS AF: 0.496 AC: 0.495605 AN: 0.495605

Gnomad4 FIN AF: 0.336 AC: 0.335521 AN: 0.335521

Gnomad4 NFE AF: 0.251 AC: 0.250803 AN: 0.250803

Gnomad4 OTH AF: 0.311 AC: 0.311366 AN: 0.311366

Alfa AF: 0.290 Hom.: 1305

Bravo AF: 0.343

Asia WGS AF: 0.527 AC: 1828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.9
DANN	Benign	0.79
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

Publications

LitVar

Other links and lift over

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