rs10459853

chr16-84383036-C-Gchr16-84383036-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014861.4(ATP2C2):c.99+14322C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,196 control chromosomes in the GnomAD database, including 1,676 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 0.14 (1676 hom., cov: 32)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

Genes affected

ATP2C2 (HGNC:29103): (ATPase secretory pathway Ca2+ transporting 2) Enables P-type calcium transporter activity and P-type manganese transporter activity. Predicted to be involved in calcium ion transmembrane transport; cellular calcium ion homeostasis; and manganese ion transport. Predicted to act upstream of or within mammary gland epithelium development; positive regulation of calcium ion import; and protein localization to plasma membrane. Predicted to be located in trans-Golgi network membrane. Predicted to be active in Golgi membrane; endoplasmic reticulum; and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2C2	NM_014861.4	c.99+14322C>G		intron_variant		ENST00000262429.9
ATP2C2	NM_001286527.3	c.99+14322C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9	c.99+14322C>G		intron_variant		1	NM_014861.4	P1
ATP2C2	ENST00000416219.6	c.99+14322C>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21597 AN: 152078 Hom.: 1680 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.142 AC: 21599 AN: 152196 Hom.: 1676 Cov.: 32 AF XY: 0.142 AC XY: 10567 AN XY: 74404

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0774 Hom.: 91

Bravo AF: 0.146

Asia WGS AF: 0.203 AC: 703 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.1
Dann	Benign	0.48

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: rs10459853; hg19: chr16-84416642;