chr16-84429919-A-G

Variant names:

• chr16-84429919-A-G
• rs962877
• NM_014861.4:c.986+4118A>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.986+4118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,048 control chromosomes in the GnomAD database, including 10,863 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 0.38 (10863 hom., cov: 32)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.72
• 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=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.986+4118A>G		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+4118A>G		intron_variant	Intron 11 of 26	1	NM_014861.4	ENSP00000262429.4
ATP2C2	ENST00000416219.7	c.986+4118A>G		intron_variant	Intron 11 of 27	1		ENSP00000397925.2
ATP2C2	ENST00000420010.6	n.659+4118A>G		intron_variant	Intron 8 of 23	2
ATP2C2	ENST00000565631.5	n.1477+4118A>G		intron_variant	Intron 9 of 24	2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56985 AN: 151930 Hom.: 10838 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.375 AC: 57070 AN: 152048 Hom.: 10863 Cov.: 32 AF XY: 0.373 AC XY: 27692 AN XY: 74318

African (AFR) AF: 0.376 AC: 15573 AN: 41434

American (AMR) AF: 0.366 AC: 5595 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1235 AN: 5180

South Asian (SAS) AF: 0.397 AC: 1909 AN: 4806

European-Finnish (FIN) AF: 0.328 AC: 3472 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26770 AN: 67990

Other (OTH) AF: 0.399 AC: 842 AN: 2112

Alfa AF: 0.382 Hom.: 6327

Bravo AF: 0.373

Asia WGS AF: 0.363 AC: 1260 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.53
DANN	Benign	0.25
PhyloP100		-3.7
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: rs962877; hg19: chr16-84463525; COSMIC: COSV52301173; COSMIC: COSV52301173;