chr5-146878727-AGCTGCT-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000530902.5(PPP2R2B):​n.162_167delAGCAGC 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 0.000966 in 1,297,202 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0051 ( 8 hom., cov: 0)
Exomes 𝑓: 0.00043 ( 2 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: Benign. The variant received -8 ACMG points.

BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00507 (763/150598) while in subpopulation AFR AF = 0.0171 (701/40998). AF 95% confidence interval is 0.016. There are 8 homozygotes in GnomAd4. There are 358 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
BS2
High AC in GnomAd4 at 763 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP2R2BNM_181675.4 linkc.-267_-262delAGCAGC 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.-267_-262delAGCAGC 5_prime_UTR_variant Exon 1 of 10 2 NM_181675.4 ENSP00000377933.3 Q00005-1

Frequencies

GnomAD3 genomes
AF:
0.00506
AC:
762
AN:
150480
Hom.:
8
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0171
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00211
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000203
Gnomad SAS
AF:
0.000425
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000237
Gnomad OTH
AF:
0.00532
GnomAD4 exome
AF:
0.000427
AC:
490
AN:
1146604
Hom.:
2
AF XY:
0.000399
AC XY:
224
AN XY:
561906
show subpopulations
African (AFR)
AF:
0.0112
AC:
260
AN:
23316
American (AMR)
AF:
0.000221
AC:
6
AN:
27132
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15240
East Asian (EAS)
AF:
0.0000420
AC:
1
AN:
23798
South Asian (SAS)
AF:
0.000110
AC:
8
AN:
72520
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
15558
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2848
European-Non Finnish (NFE)
AF:
0.000200
AC:
185
AN:
923290
Other (OTH)
AF:
0.000699
AC:
30
AN:
42902
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
27
54
81
108
135
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
22
44
66
88
110
<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:
0.00507
AC:
763
AN:
150598
Hom.:
8
Cov.:
0
AF XY:
0.00487
AC XY:
358
AN XY:
73470
show subpopulations
African (AFR)
AF:
0.0171
AC:
701
AN:
40998
American (AMR)
AF:
0.00211
AC:
32
AN:
15176
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3460
East Asian (EAS)
AF:
0.000204
AC:
1
AN:
4910
South Asian (SAS)
AF:
0.000426
AC:
2
AN:
4698
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10442
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
0.000237
AC:
16
AN:
67634
Other (OTH)
AF:
0.00527
AC:
11
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
38
75
113
150
188
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00
Hom.:
47

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.2
Mutation Taster
=299/1
polymorphism

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