chr16-84430971-G-A

Position:

• chr16-84430971-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2C2	NM_014861.4	c.986+5170G>A		intron_variant		ENST00000262429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9	c.986+5170G>A		intron_variant		1	NM_014861.4	P1
ATP2C2	ENST00000416219.6	c.986+5170G>A		intron_variant		1
ATP2C2	ENST00000420010.6	n.659+5170G>A		intron_variant, non_coding_transcript_variant		2
ATP2C2	ENST00000565631.5	n.1477+5170G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.390

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.76

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: rs8045507; hg19: chr16-84464577;