16-84416618-T-G

Variant names:

• chr16-84416618-T-G
• rs247808
• NM_014861.4:c.624+1027T>G

Variant summary

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

The NM_014861.4(ATP2C2):​c.624+1027T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,098 control chromosomes in the GnomAD database, including 47,957 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 0.79 (47957 hom., cov: 31)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	NM_014861.4	MANE Select	c.624+1027T>G		intron	N/A	NP_055676.3
	ATP2C2	NM_001286527.3		c.624+1027T>G		intron	N/A	NP_001273456.2
	ATP2C2	NM_001291454.2		c.171+1027T>G		intron	N/A	NP_001278383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.624+1027T>G		intron	N/A	ENSP00000262429.4
	ATP2C2	ENST00000416219.7	TSL:1	c.624+1027T>G		intron	N/A	ENSP00000397925.2
	ATP2C2	ENST00000420010.6	TSL:2	n.297+1027T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119909 AN: 151980 Hom.: 47946 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.789 AC: 119970 AN: 152098 Hom.: 47957 Cov.: 31 AF XY: 0.789 AC XY: 58714 AN XY: 74374

African (AFR) AF: 0.647 AC: 26819 AN: 41446

American (AMR) AF: 0.804 AC: 12299 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2874 AN: 3468

East Asian (EAS) AF: 0.892 AC: 4594 AN: 5150

South Asian (SAS) AF: 0.728 AC: 3515 AN: 4828

European-Finnish (FIN) AF: 0.890 AC: 9434 AN: 10600

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57748 AN: 68000

Other (OTH) AF: 0.785 AC: 1660 AN: 2114

Alfa AF: 0.827 Hom.: 83170

Bravo AF: 0.779

Asia WGS AF: 0.782 AC: 2722 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.48
PhyloP100		-3.2
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: rs247808; hg19: chr16-84450224;