rs1383167

Variant names:

• chr5-147018820-A-G
• rs1383167
• ENST00000394414.5:c.74+36845T>C

Variant summary

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

The ENST00000394414.5(PPP2R2B):​c.74+36845T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,064 control chromosomes in the GnomAD database, including 49,746 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 0.81 (49746 hom., cov: 32)
• Consequence: PPP2R2B ENST00000394414.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181674.3	c.74+36845T>C		intron_variant	Intron 1 of 9		NP_858060.2
PPP2R2B	NM_001271900.2	c.50+62239T>C		intron_variant	Intron 2 of 10		NP_001258829.1
PPP2R2B	NM_001271899.1	c.88+62239T>C		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+36845T>C		intron_variant	Intron 1 of 9	1		ENSP00000377936.1
PPP2R2B	ENST00000394413.7	c.50+62239T>C		intron_variant	Intron 2 of 10	2		ENSP00000377935.4
PPP2R2B	ENST00000504198.5	c.88+62239T>C		intron_variant	Intron 2 of 9	2		ENSP00000421396.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122411 AN: 151946 Hom.: 49708 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.806 AC: 122506 AN: 152064 Hom.: 49746 Cov.: 32 AF XY: 0.802 AC XY: 59578 AN XY: 74322

African (AFR) AF: 0.887 AC: 36823 AN: 41510

American (AMR) AF: 0.705 AC: 10745 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2739 AN: 3468

East Asian (EAS) AF: 0.707 AC: 3635 AN: 5144

South Asian (SAS) AF: 0.800 AC: 3859 AN: 4826

European-Finnish (FIN) AF: 0.747 AC: 7903 AN: 10574

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54149 AN: 67988

Other (OTH) AF: 0.789 AC: 1664 AN: 2108

Alfa AF: 0.796 Hom.: 26780

Bravo AF: 0.803

Asia WGS AF: 0.771 AC: 2683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.76
PhyloP100		-0.097
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: rs1383167; hg19: chr5-146398383;