dbSNP rs3808574: PPP2R2A:c.180+120T>C (chr8-26339107-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_002717.4(PPP2R2A):c.180+120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 730,466 control chromosomes in the GnomAD database, including 2,149 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 0.063 ( 468 hom., cov: 32)

Exomes 𝑓: 0.053 ( 1681 hom. )

Consequence

PPP2R2A
NM_002717.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.134

Publications

1 publications found

Variant links:

Genes affected

PPP2R2A (HGNC:9304): (protein phosphatase 2 regulatory subunit Balpha) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R2A links:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4 link	c.180+120T>C		intron_variant	Intron 3 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8 link	c.180+120T>C		intron_variant	Intron 3 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9604

AN:

152138

Hom.:

467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0866

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0902

Gnomad ASJ

AF:

0.0403

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.0983

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0757

GnomAD4 exome

AF:

0.0532

AC:

30752

AN:

578210

Hom.:

1681

AF XY:

0.0541

AC XY:

16560

AN XY:

306376

show subpopulations

African (AFR)

AF:

0.0887

AC:

1345

AN:

15170

American (AMR)

AF:

0.102

AC:

2332

AN:

22920

Ashkenazi Jewish (ASJ)

AF:

0.0454

AC:

674

AN:

14836

East Asian (EAS)

AF:

0.238

AC:

8048

AN:

33776

South Asian (SAS)

AF:

0.0894

AC:

4561

AN:

51000

European-Finnish (FIN)

AF:

0.0167

AC:

762

AN:

45674

Middle Eastern (MID)

AF:

0.0605

AC:

178

AN:

2940

European-Non Finnish (NFE)

AF:

0.0306

AC:

11074

AN:

361812

Other (OTH)

AF:

0.0591

AC:

1778

AN:

30082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1296

2593

3889

5186

6482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.0631

AC:

9614

AN:

152256

Hom.:

468

Cov.:

AF XY:

0.0635

AC XY:

4729

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0865

AC:

3596

AN:

41552

American (AMR)

AF:

0.0904

AC:

1382

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0403

AC:

140

AN:

3472

East Asian (EAS)

AF:

0.253

AC:

1308

AN:

5176

South Asian (SAS)

AF:

0.0984

AC:

475

AN:

4826

European-Finnish (FIN)

AF:

0.0179

AC:

190

AN:

10630

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0329

AC:

2240

AN:

67992

Other (OTH)

AF:

0.0758

AC:

160

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0464

Hom.:

Bravo

AF:

0.0714

Asia WGS

AF:

0.143

AC:

499

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.9

(source)

DANN

Benign

0.69

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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