Genetic Variant PPP2R2A:c.346+103G>C (chr8-26354736-G-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.346+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,143,566 control chromosomes in the GnomAD database, including 1,158 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 0.027 ( 250 hom., cov: 32)

Exomes 𝑓: 0.017 ( 908 hom. )

Consequence

PPP2R2A
NM_002717.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00500

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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 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.346+103G>C		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.376+103G>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.346+103G>C	intron	N/A	ENSP00000370113.3	P63151-1
PPP2R2A	ENST00000315985.7	TSL:2	c.376+103G>C	intron	N/A	ENSP00000325074.7	P63151-2
PPP2R2A	ENST00000919755.1		c.346+103G>C	intron	N/A	ENSP00000589814.1

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4102

AN:

152104

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0824

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00950

Gnomad OTH

AF:

0.0249

GnomAD4 exome

AF:

0.0168

AC:

16644

AN:

991344

Hom.:

908

AF XY:

0.0168

AC XY:

8096

AN XY:

482898

show subpopulations

African (AFR)

AF:

0.00301

AC:

AN:

21610

American (AMR)

AF:

0.228

AC:

3991

AN:

17488

Ashkenazi Jewish (ASJ)

AF:

0.00773

AC:

115

AN:

14876

East Asian (EAS)

AF:

0.121

AC:

3695

AN:

30592

South Asian (SAS)

AF:

0.0741

AC:

2008

AN:

27084

European-Finnish (FIN)

AF:

0.00857

AC:

301

AN:

35116

Middle Eastern (MID)

AF:

0.00609

AC:

AN:

2954

European-Non Finnish (NFE)

AF:

0.00690

AC:

5521

AN:

800472

Other (OTH)

AF:

0.0226

AC:

930

AN:

41152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

699

1399

2098

2798

3497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.0270

AC:

4115

AN:

152222

Hom.:

250

Cov.:

AF XY:

0.0300

AC XY:

2231

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00597

AC:

248

AN:

41540

American (AMR)

AF:

0.136

AC:

2072

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00779

AC:

AN:

3468

East Asian (EAS)

AF:

0.117

AC:

605

AN:

5180

South Asian (SAS)

AF:

0.0816

AC:

394

AN:

4826

European-Finnish (FIN)

AF:

0.00669

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00950

AC:

646

AN:

68002

Other (OTH)

AF:

0.0246

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

191

382

573

764

955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0221

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.105

AC:

362

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.77

PhyloP100

0.0050

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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