rs8048576

Positions:

• chr16-84389428-G-A
• chr16-84389428-G-C
• chr16-84389428-G-T

Variant summary

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

The NM_014861.4(ATP2C2):​c.100-9071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,228 control chromosomes in the GnomAD database, including 2,506 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 0.17 (2506 hom., cov: 34)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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 = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2C2	NM_014861.4	c.100-9071G>A		intron_variant		ENST00000262429.9
ATP2C2	NM_001286527.3	c.100-9071G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9	c.100-9071G>A		intron_variant		1	NM_014861.4	P1
ATP2C2	ENST00000416219.6	c.100-9071G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25674 AN: 152110 Hom.: 2489 Cov.: 34

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.169 AC: 25741 AN: 152228 Hom.: 2506 Cov.: 34 AF XY: 0.171 AC XY: 12749 AN XY: 74422

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.185

Alfa AF: 0.126 Hom.: 1798

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.68

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: rs8048576; hg19: chr16-84423034;