16-84423841-G-C

Variant names:

• chr16-84423841-G-C
• rs11860694
• NM_014861.4:c.919+578G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014861.4(ATP2C2):​c.919+578G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,082 control chromosomes in the GnomAD database, including 16,425 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 0.46 (16425 hom., cov: 33)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.919+578G>C		intron_variant	Intron 10 of 26	ENST00000262429.9	NP_055676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9	c.919+578G>C		intron_variant	Intron 10 of 26	1	NM_014861.4	ENSP00000262429.4

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69872 AN: 151964 Hom.: 16397 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.460 AC: 69962 AN: 152082 Hom.: 16425 Cov.: 33 AF XY: 0.454 AC XY: 33707 AN XY: 74326

African (AFR) AF: 0.516 AC: 21392 AN: 41468

American (AMR) AF: 0.423 AC: 6471 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1295 AN: 5178

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4818

European-Finnish (FIN) AF: 0.383 AC: 4047 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31676 AN: 67972

Other (OTH) AF: 0.483 AC: 1021 AN: 2112

Alfa AF: 0.320 Hom.: 811

Bravo AF: 0.463

Asia WGS AF: 0.377 AC: 1310 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11860694; hg19: chr16-84457447;