Variant chr16-84398569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014861.4(ATP2C2):c.170C>T(p.Ala57Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000582 in 1,460,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A57A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

ATP2C2
NM_014861.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

Variant links:

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]

ATP2C2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATP2C2	NM_014861.4 linkuse as main transcript	c.170C>T	p.Ala57Val	missense_variant	2/27	ENST00000262429.9
ATP2C2	NM_001286527.3 linkuse as main transcript	c.170C>T	p.Ala57Val	missense_variant	2/28
ATP2C2	XM_011523486.3 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/28
ATP2C2	XM_047434994.1 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9 linkuse as main transcript	c.170C>T	p.Ala57Val	missense_variant	2/27	1	NM_014861.4	P1	O75185-1
ATP2C2	ENST00000416219.6 linkuse as main transcript	c.170C>T	p.Ala57Val	missense_variant	2/28	1			O75185-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248198

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000582

AC:

AN:

1460674

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.170C>T (p.A57V) alteration is located in exon 2 (coding exon 2) of the ATP2C2 gene. This alteration results from a C to T substitution at nucleotide position 170, causing the alanine (A) at amino acid position 57 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

0.066

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.51

Sift

Benign

0.14

T;T

Sift4G

Benign

0.33

T;T

Polyphen

1.0

D;.

Vest4

0.66

MutPred

0.68

Loss of ubiquitination at K59 (P = 0.0327);Loss of ubiquitination at K59 (P = 0.0327);

MVP

0.71

ClinPred

0.94

GERP RS

5.2

Varity_R

0.30

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over