16-84405153-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

5 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4 link	c.236A>T	p.Glu79Val	missense_variant	Exon 3 of 27	ENST00000262429.9	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3 link	c.236A>T	p.Glu79Val	missense_variant	Exon 3 of 28		NP_001273456.2	O75185-3
ATP2C2	XM_011523486.3 link	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 28		XP_011521788.1
ATP2C2	XM_047434994.1 link	c.167A>T	p.Glu56Val	missense_variant	Exon 3 of 27		XP_047290950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP2C2	ENST00000262429.9 link	c.236A>T	p.Glu79Val	missense_variant	Exon 3 of 27	1	NM_014861.4	ENSP00000262429.4	O75185-1
ATP2C2	ENST00000416219.7 link	c.236A>T	p.Glu79Val	missense_variant	Exon 3 of 28	1		ENSP00000397925.2	O75185-3
ATP2C2	ENST00000565631.5 link	n.727A>T		non_coding_transcript_exon_variant	Exon 1 of 25	2
ATP2C2	ENST00000569207.5 link	n.-68A>T		upstream_gene_variant		5		ENSP00000456595.1	H3BS90

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

GnomAD2 exomes

AF:

0.000489

AC:

122

AN:

249524

AF XY:

0.000517

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 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

African (AFR)

AF:

0.000329

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00134

AC:

1493

AN:

1111986

Other (OTH)

AF:

0.000811

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000664

AC:

101

AN:

152004

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.000473

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

67976

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Aug 13, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

6.7

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

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

16-84405153-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over