Genetic Variant ATP2C2:c.986+150T>C (chr16-84425951-T-C) – 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+150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 862,502 control chromosomes in the GnomAD database, including 294,391 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 0.82 ( 52047 hom., cov: 30)

Exomes 𝑓: 0.82 ( 242344 hom. )

Consequence

ATP2C2
NM_014861.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

3 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4 link	c.986+150T>C		intron_variant	Intron 11 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.986+150T>C		intron_variant	Intron 11 of 26	1	NM_014861.4	ENSP00000262429.4		O75185-1

Frequencies

GnomAD3 genomes

AF:

0.825

AC:

125270

AN:

151914

Hom.:

52007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.823

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.842

GnomAD4 exome

AF:

0.820

AC:

582541

AN:

710470

Hom.:

242344

Cov.:

AF XY:

0.819

AC XY:

305531

AN XY:

372976

show subpopulations

African (AFR)

AF:

0.831

AC:

15597

AN:

18780

American (AMR)

AF:

0.671

AC:

24280

AN:

36200

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

15040

AN:

18222

East Asian (EAS)

AF:

0.502

AC:

17989

AN:

35862

South Asian (SAS)

AF:

0.753

AC:

47500

AN:

63104

European-Finnish (FIN)

AF:

0.851

AC:

39011

AN:

45840

Middle Eastern (MID)

AF:

0.852

AC:

2210

AN:

2594

European-Non Finnish (NFE)

AF:

0.861

AC:

391684

AN:

454686

Other (OTH)

AF:

0.831

AC:

29230

AN:

35182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4819

9637

14456

19274

24093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4778

9556

14334

19112

23890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.825

AC:

125372

AN:

152032

Hom.:

52047

Cov.:

AF XY:

0.818

AC XY:

60767

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.827

AC:

34266

AN:

41430

American (AMR)

AF:

0.753

AC:

11501

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.818

AC:

2838

AN:

3468

East Asian (EAS)

AF:

0.548

AC:

2824

AN:

5152

South Asian (SAS)

AF:

0.745

AC:

3580

AN:

4808

European-Finnish (FIN)

AF:

0.844

AC:

8938

AN:

10588

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.863

AC:

58650

AN:

67990

Other (OTH)

AF:

0.841

AC:

1774

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1081

2163

3244

4326

5407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.845

Hom.:

88063

Bravo

AF:

0.816

Asia WGS

AF:

0.677

AC:

2342

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.58

(source)

DANN

Benign

0.38

PhyloP100

-1.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over