rs11958187

chr5-147055600-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000394414.5(PPP2R2B):c.74+65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,406,188 control chromosomes in the GnomAD database, including 252,030 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 0.54 (23277 hom., cov: 30)
  • Exomes 𝑓: 0.60 (228753 hom.)
• Consequence: PPP2R2B ENST00000394414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2B	NM_001271899.1	c.88+25459C>T		intron_variant
PPP2R2B	NM_001271900.2	c.50+25459C>T		intron_variant
PPP2R2B	NM_181674.3	c.74+65C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2B	ENST00000394414.5	c.74+65C>T		intron_variant		1
PPP2R2B	ENST00000336640.10	c.79+65C>T		intron_variant		5		A1
PPP2R2B	ENST00000394413.7	c.50+25459C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82393 AN: 151624 Hom.: 23265 Cov.: 30

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.600 AC: 752484 AN: 1254446 Hom.: 228753 AF XY: 0.601 AC XY: 380916 AN XY: 633718

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.543 AC: 82447 AN: 151742 Hom.: 23277 Cov.: 30 AF XY: 0.541 AC XY: 40099 AN XY: 74146

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.582

Alfa AF: 0.609 Hom.: 29005

Bravo AF: 0.535

Asia WGS AF: 0.458 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	18
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11958187; hg19: chr5-146435163; COSMIC: COSV60758080;