rs16973771

Variant names:

• chr16-84426972-T-C
• rs16973771
• NM_014861.4:c.986+1171T>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.986+1171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,042 control chromosomes in the GnomAD database, including 11,421 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 0.38 (11421 hom., cov: 32)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014861.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	NM_014861.4	MANE Select	c.986+1171T>C		intron	N/A	NP_055676.3
	ATP2C2	NM_001286527.3		c.986+1171T>C		intron	N/A	NP_001273456.2
	ATP2C2	NM_001291454.2		c.533+1171T>C		intron	N/A	NP_001278383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.986+1171T>C		intron	N/A	ENSP00000262429.4
	ATP2C2	ENST00000416219.7	TSL:1	c.986+1171T>C		intron	N/A	ENSP00000397925.2
	ATP2C2	ENST00000861763.1		c.986+1171T>C		intron	N/A	ENSP00000531822.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58367 AN: 151924 Hom.: 11395 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.384 AC: 58451 AN: 152042 Hom.: 11421 Cov.: 32 AF XY: 0.382 AC XY: 28371 AN XY: 74328

African (AFR) AF: 0.393 AC: 16277 AN: 41456

American (AMR) AF: 0.373 AC: 5703 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1284 AN: 5174

South Asian (SAS) AF: 0.403 AC: 1940 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3487 AN: 10578

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27133 AN: 67958

Other (OTH) AF: 0.407 AC: 860 AN: 2114

Alfa AF: 0.373 Hom.: 1858

Bravo AF: 0.383

Asia WGS AF: 0.375 AC: 1301 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.40
PhyloP100		-0.61
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: rs16973771; hg19: chr16-84460578;