16-84425951-T-C

Position:

• chr16-84425951-T-C

Variant summary

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

The ENST00000262429.9(ATP2C2):​c.986+150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 862,502 control chromosomes in the GnomAD database, including 294,391 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 0.82 (52047 hom., cov: 30)
  • Exomes 𝑓: 0.82 (242344 hom.)
• Consequence: ATP2C2 ENST00000262429.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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 (NFE) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.986+150T>C		intron_variant		ENST00000262429.9	NP_055676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9	c.986+150T>C		intron_variant		1	NM_014861.4	ENSP00000262429	P1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125270 AN: 151914 Hom.: 52007 Cov.: 30

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.820 AC: 582541 AN: 710470 Hom.: 242344 Cov.: 9 AF XY: 0.819 AC XY: 305531 AN XY: 372976

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.825

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.753

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.861

Gnomad4 OTH exome AF: 0.831

GnomAD4 genome AF: 0.825 AC: 125372 AN: 152032 Hom.: 52047 Cov.: 30 AF XY: 0.818 AC XY: 60767 AN XY: 74292

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.841

Alfa AF: 0.847 Hom.: 69270

Bravo AF: 0.816

Asia WGS AF: 0.677 AC: 2342 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.58
DANN	Benign	0.38

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: rs247805; hg19: chr16-84459557;