chr5-146590061-G-A

Variant names:

• chr5-146590061-G-A
• rs141962233
• NM_181675.4:c.1218C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_181675.4(PPP2R2B):​c.1218C>T​(p.Val406Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,614,020 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: PPP2R2B NM_181675.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200

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]

ENSG00000250407 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 5-146590061-G-A is Benign according to our data. Variant chr5-146590061-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2571233.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-146590061-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.
• BS2: High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.1218C>T	p.Val406Val	synonymous_variant	Exon 10 of 10	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.1218C>T	p.Val406Val	synonymous_variant	Exon 10 of 10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.000881 AC: 134 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000681 AC: 171 AN: 251240 AF XY: 0.000700

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00118 AC: 1721 AN: 1461886 Hom.: 1 Cov.: 31 AF XY: 0.00112 AC XY: 816 AN XY: 727244

Gnomad4 AFR exome AF: 0.000179 AC: 6 AN: 33480

Gnomad4 AMR exome AF: 0.000604 AC: 27 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.0000504 AC: 2 AN: 39698

Gnomad4 SAS exome AF: 0.0000232 AC: 2 AN: 86258

Gnomad4 FIN exome AF: 0.000131 AC: 7 AN: 53420

Gnomad4 NFE exome AF: 0.00147 AC: 1638 AN: 1112006

Gnomad4 Remaining exome AF: 0.000646 AC: 39 AN: 60396

GnomAD4 genome AF: 0.000881 AC: 134 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.000834 AC XY: 62 AN XY: 74360

Gnomad4 AFR AF: 0.000241 AC: 0.000240906 AN: 0.000240906

Gnomad4 AMR AF: 0.000262 AC: 0.000262329 AN: 0.000262329

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.0000945 AC: 0.0000945358 AN: 0.0000945358

Gnomad4 NFE AF: 0.00169 AC: 0.00169078 AN: 0.00169078

Gnomad4 OTH AF: 0.00189 AC: 0.00189394 AN: 0.00189394

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.000782

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00175

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PPP2R2B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.1
DANN	Benign	0.86
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs141962233; hg19: chr5-145969624;