Genetic Variant NM_002717.4: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:

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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=-0.8).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002717.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	NM_002717.4	MANE Select	c.180+120T>C		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.210+120T>C		intron	N/A	NP_001171062.1	P63151-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP2R2A	ENST00000380737.8	TSL:1 MANE Select	c.180+120T>C	intron	N/A	ENSP00000370113.3	P63151-1
PPP2R2A	ENST00000315985.7	TSL:2	c.210+120T>C	intron	N/A	ENSP00000325074.7	P63151-2
PPP2R2A	ENST00000919755.1		c.180+120T>C	intron	N/A	ENSP00000589814.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over