chr16-84420147-A-G

Position:

• chr16-84420147-A-G

Variant summary

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

The NM_014861.4(ATP2C2):​c.625-2243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,742 control chromosomes in the GnomAD database, including 17,525 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 0.47 (17525 hom., cov: 31)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2C2	NM_014861.4	c.625-2243A>G		intron_variant		ENST00000262429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9	c.625-2243A>G		intron_variant		1	NM_014861.4	P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71887 AN: 151624 Hom.: 17497 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.474 AC: 71971 AN: 151742 Hom.: 17525 Cov.: 31 AF XY: 0.469 AC XY: 34792 AN XY: 74112

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.478

Alfa AF: 0.460 Hom.: 32998

Bravo AF: 0.477

Asia WGS AF: 0.385 AC: 1336 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.61

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: rs8053211; hg19: chr16-84453753;