16-84430303-C-T

Variant names:

• chr16-84430303-C-T
• rs2875891
• NM_014861.4:c.986+4502C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014861.4(ATP2C2):​c.986+4502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,074 control chromosomes in the GnomAD database, including 7,238 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 0.30 (7238 hom., cov: 32)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.986+4502C>T		intron_variant	Intron 11 of 26	ENST00000262429.9	NP_055676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9	c.986+4502C>T		intron_variant	Intron 11 of 26	1	NM_014861.4	ENSP00000262429.4
ATP2C2	ENST00000416219.6	c.986+4502C>T		intron_variant	Intron 11 of 27	1		ENSP00000397925.2
ATP2C2	ENST00000420010.6	n.659+4502C>T		intron_variant	Intron 8 of 23	2
ATP2C2	ENST00000565631.5	n.1477+4502C>T		intron_variant	Intron 9 of 24	2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45763 AN: 151956 Hom.: 7228 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.301 AC: 45820 AN: 152074 Hom.: 7238 Cov.: 32 AF XY: 0.301 AC XY: 22398 AN XY: 74342

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.316

Alfa AF: 0.180 Hom.: 399

Bravo AF: 0.293

Asia WGS AF: 0.278 AC: 967 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.77

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: rs2875891; hg19: chr16-84463909;