Genetic Variant PPP2R2A:c.180+130A>T (chr8-26339117-A-T) – 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+130A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 661,562 control chromosomes in the GnomAD database, including 14,985 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 0.21 ( 3709 hom., cov: 32)

Exomes 𝑓: 0.20 ( 11276 hom. )

Consequence

PPP2R2A
NM_002717.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.516

Publications

4 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4 link	c.180+130A>T		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+130A>T		intron_variant	Intron 3 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32173

AN:

152006

Hom.:

3704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.215

GnomAD4 exome

AF:

0.196

AC:

99899

AN:

509438

Hom.:

11276

AF XY:

0.195

AC XY:

52732

AN XY:

270694

show subpopulations

African (AFR)

AF:

0.275

AC:

3742

AN:

13620

American (AMR)

AF:

0.190

AC:

3682

AN:

19396

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

2332

AN:

13724

East Asian (EAS)

AF:

0.461

AC:

14938

AN:

32410

South Asian (SAS)

AF:

0.184

AC:

8648

AN:

46892

European-Finnish (FIN)

AF:

0.160

AC:

6960

AN:

43560

Middle Eastern (MID)

AF:

0.233

AC:

578

AN:

2486

European-Non Finnish (NFE)

AF:

0.173

AC:

53664

AN:

310004

Other (OTH)

AF:

0.196

AC:

5355

AN:

27346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

3627

7255

10882

14510

18137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.212

AC:

32201

AN:

152124

Hom.:

3709

Cov.:

AF XY:

0.212

AC XY:

15781

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.281

AC:

11664

AN:

41506

American (AMR)

AF:

0.175

AC:

2679

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

590

AN:

3470

East Asian (EAS)

AF:

0.423

AC:

2189

AN:

5172

South Asian (SAS)

AF:

0.203

AC:

975

AN:

4806

European-Finnish (FIN)

AF:

0.164

AC:

1738

AN:

10596

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11765

AN:

67962

Other (OTH)

AF:

0.218

AC:

460

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1284

2567

3851

5134

6418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.187

Hom.:

336

Bravo

AF:

0.217

Asia WGS

AF:

0.296

AC:

1028

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.7

(source)

DANN

Benign

0.62

PhyloP100

0.52

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