16-84405153-A-T

Position:

chr16-84405153-A-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_014861.4(ATP2C2):c.236A>T(p.Glu79Val) variant causes a missense change. The variant allele was found at a frequency of 0.00104 in 1,613,816 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

ATP2C2
NM_014861.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.72

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 16-84405153-A-T is Benign according to our data. Variant chr16-84405153-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2048303.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATP2C2	NM_014861.4 linkuse as main transcript	c.236A>T	p.Glu79Val	missense_variant	3/27	ENST00000262429.9
ATP2C2	NM_001286527.3 linkuse as main transcript	c.236A>T	p.Glu79Val	missense_variant	3/28
ATP2C2	XM_011523486.3 linkuse as main transcript	c.167A>T	p.Glu56Val	missense_variant	3/28
ATP2C2	XM_047434994.1 linkuse as main transcript	c.167A>T	p.Glu56Val	missense_variant	3/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9 linkuse as main transcript	c.236A>T	p.Glu79Val	missense_variant	3/27	1	NM_014861.4	P1	O75185-1
ATP2C2	ENST00000416219.6 linkuse as main transcript	c.236A>T	p.Glu79Val	missense_variant	3/28	1			O75185-3
ATP2C2	ENST00000565631.5 linkuse as main transcript	n.727A>T		non_coding_transcript_exon_variant	1/25	2

Frequencies

GnomAD3 genomes

AF:

0.000665

AC:

101

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000489

AC:

122

AN:

249524

Hom.:

AF XY:

0.000517

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.000945

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.00107

AC:

1570

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

766

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152004

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000473

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.000472

AC:

ExAC

AF:

0.000454

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00153

EpiControl

AF:

0.000830

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.236A>T (p.E79V) alteration is located in exon 3 (coding exon 3) of the ATP2C2 gene. This alteration results from a A to T substitution at nucleotide position 236, causing the glutamic acid (E) at amino acid position 79 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.9

D;D

REVEL

Uncertain

0.55

Sift

Benign

0.22

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.89

P;.

Vest4

0.71

MVP

0.72

ClinPred

0.059

GERP RS

5.1

Varity_R

0.16

gMVP

0.52

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

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