rs247820

Positions:

• chr16-84411831-T-C
• chr16-84411831-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.62).
• 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/exons	MANE	UniProt
ATP2C2	NM_014861.4	c.515+1066T>C		intron_variant		ENST00000262429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9	c.515+1066T>C		intron_variant		1	NM_014861.4	P1

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

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.421

Alfa AF: 0.461 Hom.: 20814

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

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: rs247820; hg19: chr16-84445437;