5-147035653-C-T

Variant names:

• chr5-147035653-C-T
• rs9325032
• ENST00000394414.5:c.74+20012G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181674.3(PPP2R2B):​c.74+20012G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,974 control chromosomes in the GnomAD database, including 35,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (35461 hom., cov: 32)
• Consequence: PPP2R2B NM_181674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 8 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181674.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2B	NM_181674.3		c.74+20012G>A		intron	N/A	NP_858060.2	Q00005-5
	PPP2R2B	NM_001271900.2		c.50+45406G>A		intron	N/A	NP_001258829.1	Q00005-4
	PPP2R2B	NM_001271899.1		c.88+45406G>A		intron	N/A	NP_001258828.1	Q00005-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2B	ENST00000394414.5	TSL:1	c.74+20012G>A		intron	N/A	ENSP00000377936.1	Q00005-5
	PPP2R2B	ENST00000394413.7	TSL:2	c.50+45406G>A		intron	N/A	ENSP00000377935.4	Q00005-4
	PPP2R2B	ENST00000504198.5	TSL:2	c.88+45406G>A		intron	N/A	ENSP00000421396.1	Q00005-3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101882 AN: 151854 Hom.: 35461 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.680

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.671 AC: 101910 AN: 151974 Hom.: 35461 Cov.: 32 AF XY: 0.671 AC XY: 49830 AN XY: 74298

African (AFR) AF: 0.496 AC: 20519 AN: 41398

American (AMR) AF: 0.621 AC: 9482 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2621 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2693 AN: 5146

South Asian (SAS) AF: 0.784 AC: 3780 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8050 AN: 10566

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52402 AN: 67980

Other (OTH) AF: 0.684 AC: 1442 AN: 2108

Alfa AF: 0.720 Hom.: 79556

Bravo AF: 0.647

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.41
DANN	Benign	0.55
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9325032; hg19: chr5-146415216;