Genetic Variant ATP2C2:c.986+1171T>C (chr16-84426972-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+1171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,042 control chromosomes in the GnomAD database, including 11,421 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 0.38 ( 11421 hom., cov: 32)

Consequence

ATP2C2
NM_014861.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.607

Publications

11 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 (SAS) allele frequency at 95% confidence interval = 0.395 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+1171T>C	intron	N/A	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3		c.986+1171T>C	intron	N/A	NP_001273456.2	O75185-3
ATP2C2	NM_001291454.2		c.533+1171T>C	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+1171T>C	intron	N/A	ENSP00000262429.4	O75185-1
ATP2C2	ENST00000416219.7	TSL:1	c.986+1171T>C	intron	N/A	ENSP00000397925.2
ATP2C2	ENST00000861763.1		c.986+1171T>C	intron	N/A	ENSP00000531822.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58367

AN:

151924

Hom.:

11395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.404

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

GnomAD4 genome

AF:

0.384

AC:

58451

AN:

152042

Hom.:

11421

Cov.:

AF XY:

0.382

AC XY:

28371

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.393

AC:

16277

AN:

41456

American (AMR)

AF:

0.373

AC:

5703

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1341

AN:

3468

East Asian (EAS)

AF:

0.248

AC:

1284

AN:

5174

South Asian (SAS)

AF:

0.403

AC:

1940

AN:

4818

European-Finnish (FIN)

AF:

0.330

AC:

3487

AN:

10578

Middle Eastern (MID)

AF:

0.339

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.399

AC:

27133

AN:

67958

Other (OTH)

AF:

0.407

AC:

860

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1884

3767

5651

7534

9418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.373

Hom.:

1858

Bravo

AF:

0.383

Asia WGS

AF:

0.375

AC:

1301

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.5

(source)

DANN

Benign

0.40

PhyloP100

-0.61

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