Genetic Variant ENST00000530902.5:n.138_167dupAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC (chr5-146878727-A-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000530902.5(PPP2R2B):n.138_167dupAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0051 ( 7 hom., cov: 0)

Exomes 𝑓: 0.0019 ( 209 hom. )

Failed GnomAD Quality Control

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 767 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4 link	c.-291_-262dupAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC		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.-291_-262dupAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	Exon 1 of 10	2	NM_181675.4	ENSP00000377933.3		Q00005-1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

769

AN:

150484

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000813

Gnomad SAS

AF:

0.00319

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.00388

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00193

AC:

2209

AN:

1146836

Hom.:

209

Cov.:

AF XY:

0.00193

AC XY:

1085

AN XY:

562020

show subpopulations

African (AFR)

AF:

0.00124

AC:

AN:

23462

American (AMR)

AF:

0.000774

AC:

AN:

27146

Ashkenazi Jewish (ASJ)

AF:

0.000328

AC:

AN:

15238

East Asian (EAS)

AF:

0.00320

AC:

AN:

23764

South Asian (SAS)

AF:

0.00139

AC:

101

AN:

72528

European-Finnish (FIN)

AF:

0.0847

AC:

1318

AN:

15556

Middle Eastern (MID)

AF:

0.00386

AC:

AN:

2848

European-Non Finnish (NFE)

AF:

0.000552

AC:

510

AN:

923394

Other (OTH)

AF:

0.00322

AC:

138

AN:

42900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.652

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00509

AC:

767

AN:

150602

Hom.:

Cov.:

AF XY:

0.00671

AC XY:

493

AN XY:

73470

show subpopulations

African (AFR)

AF:

0.00305

AC:

125

AN:

41004

American (AMR)

AF:

0.00132

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.000815

AC:

AN:

4910

South Asian (SAS)

AF:

0.00319

AC:

AN:

4700

European-Finnish (FIN)

AF:

0.0444

AC:

464

AN:

10440

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00191

AC:

129

AN:

67634

Other (OTH)

AF:

0.00384

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00666

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

(source)

Splicing

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

Publications

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ENST00000530902.5:n.138_167dupAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC

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