rs12110022

Positions:

• chr5-146770854-G-A

Variant summary

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

The NM_181675.4(PPP2R2B):​c.71-69712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,172 control chromosomes in the GnomAD database, including 421 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 0.060 (421 hom., cov: 32)
• Consequence: PPP2R2B NM_181675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.71-69712C>T		intron_variant		ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.71-69712C>T		intron_variant		2	NM_181675.4	ENSP00000377933	P3

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9080 AN: 152054 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0598 AC: 9102 AN: 152172 Hom.: 421 Cov.: 32 AF XY: 0.0594 AC XY: 4419 AN XY: 74398

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.0260

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0497 Hom.: 76

Bravo AF: 0.0635

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.19

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: rs12110022; hg19: chr5-146150417;