rs78887288

Positions:

chr16-84405221-G-A

Variant summary

Our verdict is Benign. Variant got -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. 16/20 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

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 Benign. Variant got -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: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATP2C2	NM_014861.4 linkuse as main transcript	c.304G>A	p.Val102Met	missense_variant	3/27	ENST00000262429.9	NP_055676.3
ATP2C2	NM_001286527.3 linkuse as main transcript	c.304G>A	p.Val102Met	missense_variant	3/28		NP_001273456.2
ATP2C2	XM_011523486.3 linkuse as main transcript	c.235G>A	p.Val79Met	missense_variant	3/28		XP_011521788.1
ATP2C2	XM_047434994.1 linkuse as main transcript	c.235G>A	p.Val79Met	missense_variant	3/27		XP_047290950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9 linkuse as main transcript	c.304G>A	p.Val102Met	missense_variant	3/27	1	NM_014861.4	ENSP00000262429	P1	O75185-1
ATP2C2	ENST00000416219.6 linkuse as main transcript	c.304G>A	p.Val102Met	missense_variant	3/28	1		ENSP00000397925		O75185-3
ATP2C2	ENST00000565631.5 linkuse as main transcript	n.795G>A		non_coding_transcript_exon_variant	1/25	2
ATP2C2	ENST00000569207.5 linkuse as main transcript	c.4G>A	p.Val2Met	missense_variant, NMD_transcript_variant	1/6	5		ENSP00000456595

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

GnomAD3 exomes

AF:

0.00481

AC:

1199

AN:

249070

Hom.:

AF XY:

0.00470

AC XY:

635

AN XY:

135102

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 SAS exome

AF:

0.000163

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

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00354

Gnomad4 NFE exome

AF:

0.00743

Gnomad4 OTH exome

AF:

0.00528

GnomAD4 genome

AF:

0.00465

AC:

709

AN:

152312

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00764

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00699

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

Uncertain significance, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Sep 30, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 03, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	ATP2C2: BP4, BS2 -

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

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

MutationTaster

Benign

1.0

N;N

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

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