Genetic Variant ATP2C2:c.*507C>A (chr16-84464239-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000416219.7(ATP2C2):c.*507C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 153,134 control chromosomes in the GnomAD database, including 2,449 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 0.16 ( 2428 hom., cov: 32)

Exomes 𝑓: 0.20 ( 21 hom. )

Consequence

ATP2C2
ENST00000416219.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

4 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:

ATP2C2-AS1 (HGNC:53167): (ATP2C2 antisense RNA 1)

ATP2C2-AS1 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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416219.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP2C2-AS1	NR_146503.1		n.59-1240G>T	intron	N/A
ATP2C2	NM_014861.4	MANE Select	c.*507C>A	downstream_gene	N/A	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3		c.*507C>A	downstream_gene	N/A	NP_001273456.2	O75185-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATP2C2	ENST00000416219.7	TSL:1	c.*507C>A	3_prime_UTR	Exon 28 of 28	ENSP00000397925.2
ATP2C2-AS1	ENST00000565700.1	TSL:1	n.59-1240G>T	intron	N/A
ATP2C2	ENST00000861763.1		c.*507C>A	3_prime_UTR	Exon 28 of 28	ENSP00000531822.1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24179

AN:

151864

Hom.:

2429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.198

AC:

228

AN:

1150

Hom.:

AF XY:

0.208

AC XY:

125

AN XY:

600

show subpopulations

African (AFR)

AF:

0.0714

AC:

AN:

American (AMR)

AF:

0.200

AC:

AN:

170

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.143

AC:

AN:

South Asian (SAS)

AF:

0.185

AC:

AN:

European-Finnish (FIN)

AF:

0.286

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.196

AC:

157

AN:

800

Other (OTH)

AF:

0.286

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.159

AC:

24183

AN:

151984

Hom.:

2428

Cov.:

AF XY:

0.164

AC XY:

12186

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0478

AC:

1981

AN:

41402

American (AMR)

AF:

0.190

AC:

2900

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

760

AN:

3472

East Asian (EAS)

AF:

0.0855

AC:

441

AN:

5158

South Asian (SAS)

AF:

0.208

AC:

1006

AN:

4826

European-Finnish (FIN)

AF:

0.269

AC:

2847

AN:

10576

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13677

AN:

67958

Other (OTH)

AF:

0.152

AC:

320

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

993

1986

2979

3972

4965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.182

Hom.:

7671

Bravo

AF:

0.147

Asia WGS

AF:

0.128

AC:

446

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.62

(source)

DANN

Benign

0.76

PhyloP100

-1.8

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over