Genetic Variant PPP2R2A:c.82+57A>G (chr8-26293797-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002717.4(PPP2R2A):c.82+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,499,618 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 50 hom. )

Consequence

PPP2R2A
NM_002717.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0820

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-26293797-A-G is Benign according to our data. Variant chr8-26293797-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1679063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 418 AD gene.

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.82+57A>G		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.112+57A>G		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.82+57A>G	intron	N/A	ENSP00000370113.3	P63151-1
PPP2R2A	ENST00000315985.7	TSL:2	c.112+57A>G	intron	N/A	ENSP00000325074.7	P63151-2
PPP2R2A	ENST00000919755.1		c.82+57A>G	intron	N/A	ENSP00000589814.1

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

421

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00512

AC:

1213

AN:

236958

AF XY:

0.00577

show subpopulations

Gnomad AFR exome

AF:

0.000198

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.0313

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00274

Gnomad NFE exome

AF:

0.00306

Gnomad OTH exome

AF:

0.00720

GnomAD4 exome

AF:

0.00363

AC:

4887

AN:

1347284

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

2754

AN XY:

676180

show subpopulations

African (AFR)

AF:

0.000520

AC:

AN:

30766

American (AMR)

AF:

0.00236

AC:

104

AN:

43982

Ashkenazi Jewish (ASJ)

AF:

0.0315

AC:

800

AN:

25388

East Asian (EAS)

AF:

0.00

AC:

AN:

38708

South Asian (SAS)

AF:

0.0129

AC:

1069

AN:

83182

European-Finnish (FIN)

AF:

0.00228

AC:

118

AN:

51654

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.00238

AC:

2403

AN:

1011536

Other (OTH)

AF:

0.00557

AC:

315

AN:

56526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

228

456

684

912

1140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.00274

AC:

418

AN:

152334

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41578

American (AMR)

AF:

0.00255

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.0126

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00260

AC:

177

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00495

Hom.:

Bravo

AF:

0.00270

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary breast ovarian cancer syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.34

PhyloP100

-0.082

PromoterAI

0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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