chr16-84373822-G-C

Variant names:

• chr16-84373822-G-C
• rs17740111
• NM_014861.4:c.99+5108G>C

Variant summary

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

The NM_014861.4(ATP2C2):​c.99+5108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,142 control chromosomes in the GnomAD database, including 2,283 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 0.17 (2283 hom., cov: 33)
• Consequence: ATP2C2 NM_014861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 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.99+5108G>C		intron	N/A	NP_055676.3
	ATP2C2	NM_001286527.3		c.99+5108G>C		intron	N/A	NP_001273456.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.99+5108G>C		intron	N/A	ENSP00000262429.4
	ATP2C2	ENST00000416219.7	TSL:1	c.99+5108G>C		intron	N/A	ENSP00000397925.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25222 AN: 152026 Hom.: 2290 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.166 AC: 25216 AN: 152142 Hom.: 2283 Cov.: 33 AF XY: 0.167 AC XY: 12383 AN XY: 74360

African (AFR) AF: 0.112 AC: 4634 AN: 41512

American (AMR) AF: 0.144 AC: 2202 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1479 AN: 5180

South Asian (SAS) AF: 0.172 AC: 830 AN: 4818

European-Finnish (FIN) AF: 0.195 AC: 2058 AN: 10570

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13059 AN: 67996

Other (OTH) AF: 0.157 AC: 332 AN: 2114

Alfa AF: 0.0697 Hom.: 102

Bravo AF: 0.159

Asia WGS AF: 0.210 AC: 728 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.40
PhyloP100		-0.26
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: rs17740111; hg19: chr16-84407428;