3-10443042-C-T

Variant names:

• chr3-10443042-C-T
• rs17603886
• NM_001001331.4:c.199+6303G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001001331.4(ATP2B2):​c.199+6303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 152,302 control chromosomes in the GnomAD database, including 87 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 0.030 (87 hom., cov: 32)
• Consequence: ATP2B2 NM_001001331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0301 (4589/152302) while in subpopulation NFE AF= 0.0349 (2371/68022). AF 95% confidence interval is 0.0337. There are 87 homozygotes in gnomad4. There are 2201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4589 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B2	NM_001001331.4	c.199+6303G>A		intron_variant	Intron 2 of 22	ENST00000360273.7	NP_001001331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B2	ENST00000360273.7	c.199+6303G>A		intron_variant	Intron 2 of 22	5	NM_001001331.4	ENSP00000353414.2

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4588 AN: 152184 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0301 AC: 4589 AN: 152302 Hom.: 87 Cov.: 32 AF XY: 0.0295 AC XY: 2201 AN XY: 74484

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0330 Hom.: 94

Bravo AF: 0.0307

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.77

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: rs17603886; hg19: chr3-10484726;