GeneBe

rs10591869

Variant names:

Variant summary

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

The ENST00000530902.5(PPP2R2B):​n.144_167delAGCAGCAGCAGCAGCAGCAGCAGC 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 0.0000105 in 1,147,002 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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: not found (cov: 0)
Exomes 𝑓: 0.000010 ( 0 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)

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 GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP2R2BNM_181675.4 linkc.-285_-262delAGCAGCAGCAGCAGCAGCAGCAGC 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
PPP2R2BENST00000394411.9 linkc.-285_-262delAGCAGCAGCAGCAGCAGCAGCAGC 5_prime_UTR_variant Exon 1 of 10 2 NM_181675.4 ENSP00000377933.3 Q00005-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.0000105
AC:
12
AN:
1147002
Hom.:
0
AF XY:
0.0000142
AC XY:
8
AN XY:
562108
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
23470
American (AMR)
AF:
0.00
AC:
0
AN:
27150
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15244
East Asian (EAS)
AF:
0.00
AC:
0
AN:
23798
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72538
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
15564
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2848
European-Non Finnish (NFE)
AF:
0.0000119
AC:
11
AN:
923476
Other (OTH)
AF:
0.0000233
AC:
1
AN:
42914
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
0
Alfa
AF:
0.00
Hom.:
47

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.2

Splicing

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

Publications

Other links and lift over

dbSNP: rs10591869; hg19: chr5-146258290; API