rs1383169

Variant names:

• chr5-147055237-C-T
• rs1383169
• ENST00000394414.5:c.74+428G>A

Variant summary

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

The ENST00000394414.5(PPP2R2B):​c.74+428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,090 control chromosomes in the GnomAD database, including 5,567 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 0.21 (5567 hom., cov: 33)
• Consequence: PPP2R2B ENST00000394414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 1 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)

ENSG00000286468 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181674.3	c.74+428G>A		intron_variant	Intron 1 of 9		NP_858060.2
PPP2R2B	NM_001271900.2	c.50+25822G>A		intron_variant	Intron 2 of 10		NP_001258829.1
PPP2R2B	NM_001271899.1	c.88+25822G>A		intron_variant	Intron 2 of 9		NP_001258828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394414.5	c.74+428G>A		intron_variant	Intron 1 of 9	1		ENSP00000377936.1
PPP2R2B	ENST00000394413.7	c.50+25822G>A		intron_variant	Intron 2 of 10	2		ENSP00000377935.4
PPP2R2B	ENST00000504198.5	c.88+25822G>A		intron_variant	Intron 2 of 9	2		ENSP00000421396.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32502 AN: 151974 Hom.: 5561 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0869

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.214 AC: 32550 AN: 152090 Hom.: 5567 Cov.: 33 AF XY: 0.216 AC XY: 16061 AN XY: 74338

African (AFR) AF: 0.450 AC: 18650 AN: 41446

American (AMR) AF: 0.172 AC: 2632 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2214 AN: 5148

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4824

European-Finnish (FIN) AF: 0.0963 AC: 1020 AN: 10590

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0869 AC: 5912 AN: 68010

Other (OTH) AF: 0.200 AC: 423 AN: 2114

Alfa AF: 0.130 Hom.: 3930

Bravo AF: 0.227

Asia WGS AF: 0.337 AC: 1169 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.64
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1383169; hg19: chr5-146434800; COSMIC: COSV107407841;