rs78887288

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014861.4(ATP2C2):c.304G>A(p.Val102Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 1,614,018 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 38 hom. )

Consequence

ATP2C2
NM_014861.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.948

Publications

10 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024264753).

BP6

Variant 16-84405221-G-A is Benign according to our data. Variant chr16-84405221-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 547871.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

BS2

High Homozygotes in GnomAdExome4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4 link	c.304G>A	p.Val102Met	missense_variant	Exon 3 of 27	ENST00000262429.9	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3 link	c.304G>A	p.Val102Met	missense_variant	Exon 3 of 28		NP_001273456.2	O75185-3
ATP2C2	XM_011523486.3 link	c.235G>A	p.Val79Met	missense_variant	Exon 3 of 28		XP_011521788.1
ATP2C2	XM_047434994.1 link	c.235G>A	p.Val79Met	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.304G>A	p.Val102Met	missense_variant	Exon 3 of 27	1	NM_014861.4	ENSP00000262429.4	O75185-1
ATP2C2	ENST00000416219.7 link	c.304G>A	p.Val102Met	missense_variant	Exon 3 of 28	1		ENSP00000397925.2	O75185-3
ATP2C2	ENST00000565631.5 link	n.795G>A		non_coding_transcript_exon_variant	Exon 1 of 25	2
ATP2C2	ENST00000569207.5 link	n.1G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000456595.1	H3BS90

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

709

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00764

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.00481

AC:

1199

AN:

249070

AF XY:

0.00470

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00344

Gnomad NFE exome

AF:

0.00754

Gnomad OTH exome

AF:

0.00463

GnomAD4 exome

AF:

0.00636

AC:

9299

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

4528

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33478

American (AMR)

AF:

0.00391

AC:

175

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

280

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000255

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00354

AC:

189

AN:

53408

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00743

AC:

8259

AN:

1111884

Other (OTH)

AF:

0.00528

AC:

319

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

477

955

1432

1910

2387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00465

AC:

709

AN:

152312

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

41564

American (AMR)

AF:

0.00536

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00764

AC:

520

AN:

68036

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00657

Hom.:

Bravo

AF:

0.00463

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00170

AC:

ESP6500EA

AF:

0.00665

AC:

ExAC

AF:

0.00465

AC:

563

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.00676

EpiControl

AF:

0.00652

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Sep 30, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ATP2C2: BP4, BS2 -

Dec 03, 2018

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

0.087

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.5

L;L

PhyloP100

0.95

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.12

Sift

Benign

0.079

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.011

B;.

Vest4

0.32

MVP

0.42

ClinPred

0.0043

GERP RS

2.0

Varity_R

0.021

gMVP

0.31

Mutation Taster

=99/1

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

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rs78887288

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