5-147035653-C-T

Position:

• chr5-147035653-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394414.5(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 ENST00000394414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_001271899.1	c.88+45406G>A		intron_variant			NP_001258828.1
PPP2R2B	NM_001271900.2	c.50+45406G>A		intron_variant			NP_001258829.1
PPP2R2B	NM_181674.3	c.74+20012G>A		intron_variant			NP_858060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394414.5	c.74+20012G>A		intron_variant		1		ENSP00000377936
PPP2R2B	ENST00000336640.10	c.79+20012G>A		intron_variant		5		ENSP00000336591	A1
PPP2R2B	ENST00000394413.7	c.50+45406G>A		intron_variant		2		ENSP00000377935

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

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.684

Alfa AF: 0.743 Hom.: 51003

Bravo AF: 0.647

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.41
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9325032; hg19: chr5-146415216;