Genetic Variant ATP2C2:c.515+1066T>C (chr16-84411831-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.515+1066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,114 control chromosomes in the GnomAD database, including 14,445 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 0.43 ( 14445 hom., cov: 33)

Consequence

ATP2C2
NM_014861.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.263

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=-0.62).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 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.515+1066T>C	intron	N/A	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3		c.515+1066T>C	intron	N/A	NP_001273456.2	O75185-3
ATP2C2	NM_001291454.2		c.62+1228T>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.515+1066T>C	intron	N/A	ENSP00000262429.4	O75185-1
ATP2C2	ENST00000416219.7	TSL:1	c.515+1066T>C	intron	N/A	ENSP00000397925.2
ATP2C2	ENST00000861763.1		c.515+1066T>C	intron	N/A	ENSP00000531822.1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65271

AN:

151996

Hom.:

14436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.422

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

GnomAD4 genome

AF:

0.429

AC:

65303

AN:

152114

Hom.:

14445

Cov.:

AF XY:

0.426

AC XY:

31662

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.350

AC:

14503

AN:

41494

American (AMR)

AF:

0.370

AC:

5651

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1532

AN:

3472

East Asian (EAS)

AF:

0.383

AC:

1988

AN:

5184

South Asian (SAS)

AF:

0.483

AC:

2327

AN:

4814

European-Finnish (FIN)

AF:

0.443

AC:

4674

AN:

10560

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.489

AC:

33241

AN:

67990

Other (OTH)

AF:

0.421

AC:

887

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1873

3746

5618

7491

9364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.461

Hom.:

24816

Bravo

AF:

0.416

Asia WGS

AF:

0.423

AC:

1470

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-0.26

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