rs8045507

Variant names:

• chr16-84430971-G-A
• rs8045507
• NM_014861.4:c.986+5170G>A

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+5170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,742 control chromosomes in the GnomAD database, including 10,377 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 0.37 (10377 hom., cov: 30)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 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+5170G>A		intron	N/A	NP_055676.3	O75185-1
	ATP2C2	NM_001286527.3		c.986+5170G>A		intron	N/A	NP_001273456.2	O75185-3
	ATP2C2	NM_001291454.2		c.533+5170G>A		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+5170G>A		intron	N/A	ENSP00000262429.4	O75185-1
	ATP2C2	ENST00000416219.7	TSL:1	c.986+5170G>A		intron	N/A	ENSP00000397925.2
	ATP2C2	ENST00000861763.1		c.1061+1725G>A		intron	N/A	ENSP00000531822.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55615 AN: 151624 Hom.: 10353 Cov.: 30

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.367 AC: 55698 AN: 151742 Hom.: 10377 Cov.: 30 AF XY: 0.364 AC XY: 27022 AN XY: 74180

African (AFR) AF: 0.347 AC: 14358 AN: 41342

American (AMR) AF: 0.363 AC: 5532 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1188 AN: 5154

South Asian (SAS) AF: 0.394 AC: 1890 AN: 4802

European-Finnish (FIN) AF: 0.328 AC: 3456 AN: 10546

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26721 AN: 67878

Other (OTH) AF: 0.390 AC: 821 AN: 2106

Alfa AF: 0.367 Hom.: 1279

Bravo AF: 0.363

Asia WGS AF: 0.356 AC: 1236 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.76
PhyloP100		-0.63
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: rs8045507; hg19: chr16-84464577;