16-84411831-T-C

Variant names:

• chr16-84411831-T-C
• rs247820
• NM_014861.4:c.515+1066T>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.515+1066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,114 control chromosomes in the GnomAD database, including 14,445 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 0.43 (14445 hom., cov: 33)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 3 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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.515+1066T>C		intron_variant	Intron 6 of 26	ENST00000262429.9	NP_055676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9	c.515+1066T>C		intron_variant	Intron 6 of 26	1	NM_014861.4	ENSP00000262429.4

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65271 AN: 151996 Hom.: 14436 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.429 AC: 65303 AN: 152114 Hom.: 14445 Cov.: 33 AF XY: 0.426 AC XY: 31662 AN XY: 74352

African (AFR) AF: 0.350 AC: 14503 AN: 41494

American (AMR) AF: 0.370 AC: 5651 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3472

East Asian (EAS) AF: 0.383 AC: 1988 AN: 5184

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4814

European-Finnish (FIN) AF: 0.443 AC: 4674 AN: 10560

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.489 AC: 33241 AN: 67990

Other (OTH) AF: 0.421 AC: 887 AN: 2108

Alfa AF: 0.461 Hom.: 24816

Bravo AF: 0.416

Asia WGS AF: 0.423 AC: 1470 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		-0.26
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: rs247820; hg19: chr16-84445437;