NM_014861.4:c.515+2013C>G

Variant names:

• chr16-84412778-C-G
• rs10514604
• NM_014861.4:c.515+2013C>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.515+2013C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,780 control chromosomes in the GnomAD database, including 19,455 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 0.49 (19455 hom., cov: 31)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.515+2013C>G		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+2013C>G		intron_variant	Intron 6 of 26	1	NM_014861.4	ENSP00000262429.4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74585 AN: 151662 Hom.: 19452 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.492 AC: 74613 AN: 151780 Hom.: 19455 Cov.: 31 AF XY: 0.492 AC XY: 36512 AN XY: 74166

African (AFR) AF: 0.335 AC: 13876 AN: 41412

American (AMR) AF: 0.467 AC: 7112 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1931 AN: 3458

East Asian (EAS) AF: 0.365 AC: 1882 AN: 5150

South Asian (SAS) AF: 0.386 AC: 1851 AN: 4792

European-Finnish (FIN) AF: 0.606 AC: 6370 AN: 10520

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.589 AC: 39965 AN: 67900

Other (OTH) AF: 0.503 AC: 1060 AN: 2106

Alfa AF: 0.547 Hom.: 12057

Bravo AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.64
PhyloP100		-1.0
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: rs10514604; hg19: chr16-84446384;