rs371388

Positions:

• chr5-146682504-A-T

Variant summary

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

The NM_181675.4(PPP2R2B):​c.447+8624T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,248 control chromosomes in the GnomAD database, including 1,243 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 0.079 (1243 hom., cov: 32)
• Consequence: PPP2R2B NM_181675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2B	NM_181675.4	c.447+8624T>A		intron_variant		ENST00000394411.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.447+8624T>A		intron_variant		2	NM_181675.4	P3

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12023 AN: 152130 Hom.: 1239 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0792 AC: 12059 AN: 152248 Hom.: 1243 Cov.: 32 AF XY: 0.0758 AC XY: 5642 AN XY: 74456

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0544 Hom.: 106

Bravo AF: 0.0888

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs371388; hg19: chr5-146062067;