5-146854076-C-T

Variant names:

• chr5-146854076-C-T
• rs10477313
• NM_181675.4:c.70+23926G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181675.4(PPP2R2B):​c.70+23926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,892 control chromosomes in the GnomAD database, including 2,805 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 0.18 (2805 hom., cov: 32)
• Consequence: PPP2R2B NM_181675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 12

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.70+23926G>A		intron_variant	Intron 2 of 9	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.70+23926G>A		intron_variant	Intron 2 of 9	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26780 AN: 151772 Hom.: 2804 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.176 AC: 26803 AN: 151892 Hom.: 2805 Cov.: 32 AF XY: 0.179 AC XY: 13300 AN XY: 74228

African (AFR) AF: 0.249 AC: 10311 AN: 41420

American (AMR) AF: 0.198 AC: 3014 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1789 AN: 5146

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4812

European-Finnish (FIN) AF: 0.0994 AC: 1050 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7902 AN: 67920

Other (OTH) AF: 0.182 AC: 383 AN: 2104

Alfa AF: 0.142 Hom.: 7493

Bravo AF: 0.186

Asia WGS AF: 0.310 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.42
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10477313; hg19: chr5-146233639;