Genetic Variant ATP2C2:c.986+4502C>T (chr16-84430303-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014861.4(ATP2C2):c.986+4502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,074 control chromosomes in the GnomAD database, including 7,238 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7238 hom., cov: 32)

Consequence

ATP2C2
NM_014861.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.531

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014861.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP2C2	NM_014861.4	MANE Select	c.986+4502C>T	intron	N/A	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3		c.986+4502C>T	intron	N/A	NP_001273456.2	O75185-3
ATP2C2	NM_001291454.2		c.533+4502C>T	intron	N/A	NP_001278383.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.986+4502C>T	intron	N/A	ENSP00000262429.4	O75185-1
ATP2C2	ENST00000416219.7	TSL:1	c.986+4502C>T	intron	N/A	ENSP00000397925.2
ATP2C2	ENST00000861763.1		c.1061+1057C>T	intron	N/A	ENSP00000531822.1

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45763

AN:

151956

Hom.:

7228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.301

AC:

45820

AN:

152074

Hom.:

7238

Cov.:

AF XY:

0.301

AC XY:

22398

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.232

AC:

9618

AN:

41480

American (AMR)

AF:

0.299

AC:

4572

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1074

AN:

3470

East Asian (EAS)

AF:

0.164

AC:

851

AN:

5174

South Asian (SAS)

AF:

0.348

AC:

1677

AN:

4820

European-Finnish (FIN)

AF:

0.306

AC:

3242

AN:

10578

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23785

AN:

67976

Other (OTH)

AF:

0.316

AC:

666

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1658

3316

4973

6631

8289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.180

Hom.:

399

Bravo

AF:

0.293

Asia WGS

AF:

0.278

AC:

967

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.4

(source)

DANN

Benign

0.77

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over