rs1864982

Positions:

• chr5-146941260-G-T

Variant summary

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

The NM_181674.3(PPP2R2B):​c.75-63065C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,958 control chromosomes in the GnomAD database, including 4,393 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 0.22 (4393 hom., cov: 32)
• Consequence: PPP2R2B NM_181674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181674.3	c.75-63065C>A		intron_variant			NP_858060.2
PPP2R2B	NM_001271900.2	c.51-63065C>A		intron_variant			NP_001258829.1
PPP2R2B	NM_001271899.1	c.88+139799C>A		intron_variant			NP_001258828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394414.5	c.75-63065C>A		intron_variant		1		ENSP00000377936.1
PPP2R2B	ENST00000394413.7	c.51-63065C>A		intron_variant		2		ENSP00000377935.4
PPP2R2B	ENST00000504198.5	c.88+139799C>A		intron_variant		2		ENSP00000421396.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32838 AN: 151840 Hom.: 4383 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.216 AC: 32864 AN: 151958 Hom.: 4393 Cov.: 32 AF XY: 0.217 AC XY: 16091 AN XY: 74252

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.217

Alfa AF: 0.154 Hom.: 4669

Bravo AF: 0.232

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1864982; hg19: chr5-146320823;