Genetic Variant PPP2R2B:n.159_167dupAGCAGCAGC (chr5-146878727-A-AGCTGCTGCT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000530902.5(PPP2R2B):n.159_167dupAGCAGCAGC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,289,898 control chromosomes in the GnomAD database, including 7,109 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1619 hom., cov: 0)

Exomes 𝑓: 0.13 ( 5490 hom. )

Consequence

PPP2R2B
ENST00000530902.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

Publications

4 publications found

Variant links:

Genes affected

PPP2R2B (HGNC:9305): (protein phosphatase 2 regulatory subunit Bbeta) 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 a beta isoform of the regulatory subunit B55 subfamily. Defects in this gene cause autosomal dominant spinocerebellar ataxia 12 (SCA12), a disease caused by degeneration of the cerebellum, sometimes involving the brainstem and spinal cord, and in resulting in poor coordination of speech and body movements. Multiple alternatively spliced variants, which encode different isoforms, have been identified for this gene. The 5' UTR of some of these variants includes a CAG trinucleotide repeat sequence (7-28 copies) that can be expanded to 55-78 copies in cases of SCA12. [provided by RefSeq, Jul 2016]

PPP2R2B Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 12
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

PPP2R2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4 link	c.-270_-262dupAGCAGCAGC		5_prime_UTR_variant	Exon 1 of 10	ENST00000394411.9	NP_858061.3	Q00005-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9 link	c.-270_-262dupAGCAGCAGC		5_prime_UTR_variant	Exon 1 of 10	2	NM_181675.4	ENSP00000377933.3		Q00005-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21147

AN:

150410

Hom.:

1617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.0819

Gnomad MID

AF:

0.186

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.125

AC:

142786

AN:

1139370

Hom.:

5490

Cov.:

AF XY:

0.128

AC XY:

71407

AN XY:

558292

show subpopulations

African (AFR)

AF:

0.159

AC:

3632

AN:

22880

American (AMR)

AF:

0.198

AC:

5342

AN:

26916

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

3424

AN:

15086

East Asian (EAS)

AF:

0.157

AC:

3587

AN:

22916

South Asian (SAS)

AF:

0.202

AC:

14501

AN:

71856

European-Finnish (FIN)

AF:

0.0878

AC:

1352

AN:

15390

Middle Eastern (MID)

AF:

0.174

AC:

489

AN:

2806

European-Non Finnish (NFE)

AF:

0.114

AC:

104365

AN:

918954

Other (OTH)

AF:

0.143

AC:

6094

AN:

42566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

4808

9615

14423

19230

24038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.141

AC:

21167

AN:

150528

Hom.:

1619

Cov.:

AF XY:

0.141

AC XY:

10351

AN XY:

73434

show subpopulations

African (AFR)

AF:

0.152

AC:

6207

AN:

40966

American (AMR)

AF:

0.165

AC:

2504

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

735

AN:

3460

East Asian (EAS)

AF:

0.277

AC:

1359

AN:

4902

South Asian (SAS)

AF:

0.200

AC:

940

AN:

4700

European-Finnish (FIN)

AF:

0.0819

AC:

855

AN:

10436

Middle Eastern (MID)

AF:

0.186

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.117

AC:

7941

AN:

67614

Other (OTH)

AF:

0.162

AC:

338

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

886

1772

2659

3545

4431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0634

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

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