Genetic Variant PPP2R2B:n.167_168insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC (chr5-146878727-A-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT) – 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.167_168insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC 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 0.00043 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00021 ( 10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 65 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4 link	c.-262_-261insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	Exon 1 of 10	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9 link	c.-262_-261insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC		5_prime_UTR_variant	Exon 1 of 10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes

AF:

0.000432

AC:

AN:

150486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00142

Gnomad SAS

AF:

0.00106

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000211

AC:

242

AN:

1146902

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

141

AN XY:

562066

show subpopulations

African (AFR)

AF:

0.000511

AC:

AN:

23468

American (AMR)

AF:

0.000405

AC:

AN:

27148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15244

East Asian (EAS)

AF:

0.00214

AC:

AN:

23784

South Asian (SAS)

AF:

0.000786

AC:

AN:

72528

European-Finnish (FIN)

AF:

0.000257

AC:

AN:

15562

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

2848

European-Non Finnish (NFE)

AF:

0.0000985

AC:

AN:

923410

Other (OTH)

AF:

0.000350

AC:

AN:

42910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000432

AC:

AN:

150604

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

AN XY:

73472

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

41004

American (AMR)

AF:

0.000132

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00143

AC:

AN:

4910

South Asian (SAS)

AF:

0.00106

AC:

AN:

4700

European-Finnish (FIN)

AF:

0.000192

AC:

AN:

10442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67632

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over