16-84408489-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014861.4(ATP2C2):c.412G>A(p.Ala138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,612,442 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 28 hom. )

Consequence

ATP2C2
NM_014861.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.240

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009264618).

BP6

Variant 16-84408489-G-A is Benign according to our data. Variant chr16-84408489-G-A is described in ClinVar as [Benign]. Clinvar id is 779452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00384 (5603/1460446) while in subpopulation AMR AF = 0.0178 (798/44718). AF 95% confidence interval is 0.0168. There are 28 homozygotes in GnomAdExome4. There are 2604 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4 link	c.412G>A	p.Ala138Thr	missense_variant	Exon 4 of 27	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.412G>A	p.Ala138Thr	missense_variant	Exon 4 of 27	1	NM_014861.4	ENSP00000262429.4		O75185-1

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

538

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00388

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00796

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.00589

AC:

1459

AN:

247790

AF XY:

0.00499

show subpopulations

Gnomad AFR exome

AF:

0.00260

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.00723

Gnomad NFE exome

AF:

0.00398

Gnomad OTH exome

AF:

0.00563

GnomAD4 exome

AF:

0.00384

AC:

5603

AN:

1460446

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

2604

AN XY:

726528

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

33474

American (AMR)

AF:

0.0178

AC:

798

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

26132

East Asian (EAS)

AF:

0.00164

AC:

AN:

39696

South Asian (SAS)

AF:

0.000406

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00960

AC:

502

AN:

52282

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00349

AC:

3877

AN:

1111778

Other (OTH)

AF:

0.00355

AC:

214

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

255

509

764

1018

1273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00357

AC:

543

AN:

151996

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

254

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.00285

AC:

118

AN:

41446

American (AMR)

AF:

0.00537

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00389

AC:

AN:

5140

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00796

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00332

AC:

226

AN:

67984

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00376

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00287

AC:

ESP6500EA

AF:

0.00355

AC:

ExAC

AF:

0.00596

AC:

722

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.00278

EpiControl

AF:

0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

0.34

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

-0.080

N;N

PhyloP100

-0.24

PrimateAI

Benign

0.37

PROVEAN

Benign

2.2

N;N

REVEL

Uncertain

0.33

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;.

Vest4

0.35

MVP

0.28

ClinPred

0.00024

GERP RS

-0.14

Varity_R

0.044

gMVP

0.55

Mutation Taster

=73/27

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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16-84408489-G-A

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