rs4782970

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 3P and 12B. PVS1_ModeratePP3BP6_Very_StrongBS2

The NM_014861.4(ATP2C2):c.2482-2A>C variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00838 in 1,613,792 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0085 ( 98 hom. )

Consequence

ATP2C2
NM_014861.4 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 8.24

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:

ATP2C2-AS1 (HGNC:53167): (ATP2C2 antisense RNA 1)

ATP2C2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.034846883 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Multiple lines of computational evidence support a deleterious effect 6: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen, phyloP100way_vertebrate [when BayesDel_addAF, MutationTaster was below the threshold]

BP6

Variant 16-84461712-A-C is Benign according to our data. Variant chr16-84461712-A-C is described in ClinVar as [Benign]. Clinvar id is 789227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4 link	c.2482-2A>C		splice_acceptor_variant, intron_variant	Intron 24 of 26	ENST00000262429.9	NP_055676.3	O75185-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9 link	c.2482-2A>C		splice_acceptor_variant, intron_variant	Intron 24 of 26	1	NM_014861.4	ENSP00000262429.4		O75185-1

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1165

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00978

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00874

AC:

2181

AN:

249480

Hom.:

AF XY:

0.00912

AC XY:

1234

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.000903

Gnomad AMR exome

AF:

0.00539

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00578

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00990

GnomAD4 exome

AF:

0.00846

AC:

12361

AN:

1461480

Hom.:

Cov.:

AF XY:

0.00845

AC XY:

6147

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00574

Gnomad4 FIN exome

AF:

0.0224

Gnomad4 NFE exome

AF:

0.00878

Gnomad4 OTH exome

AF:

0.00836

GnomAD4 genome

AF:

0.00764

AC:

1164

AN:

152312

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

624

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0273

Gnomad4 NFE

AF:

0.00978

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00896

Hom.:

Bravo

AF:

0.00579

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000927

AC:

ESP6500EA

AF:

0.00997

AC:

ExAC

AF:

0.00843

AC:

1022

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.0101

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATP2C2: BS1, BS2; ATP2C2-AS1: BS1, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ATP2C2-related disorder

Benign:1

Aug 31, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

GERP RS

5.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.73

Position offset: 12

DS_AL_spliceai

1.0

Position offset: 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