rs11744339

Variant names:

• chr5-146598518-A-G
• rs11744339
• NM_181675.4:c.960+1773T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-146598518-A-G
• chr5-146598518-A-T

Variant summary

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

The NM_181675.4(PPP2R2B):​c.960+1773T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 152,250 control chromosomes in the GnomAD database, including 831 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 0.087 (831 hom., cov: 32)
• Consequence: PPP2R2B NM_181675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 4 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)

ENSG00000250407 (HGNC:58421):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.960+1773T>C		intron_variant	Intron 8 of 9	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.960+1773T>C		intron_variant	Intron 8 of 9	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13260 AN: 152132 Hom.: 833 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0870 AC: 13252 AN: 152250 Hom.: 831 Cov.: 32 AF XY: 0.0879 AC XY: 6542 AN XY: 74434

African (AFR) AF: 0.0231 AC: 959 AN: 41562

American (AMR) AF: 0.0719 AC: 1100 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 281 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0275 AC: 133 AN: 4832

European-Finnish (FIN) AF: 0.164 AC: 1734 AN: 10576

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8792 AN: 68008

Other (OTH) AF: 0.0776 AC: 164 AN: 2114

Alfa AF: 0.0641 Hom.: 100

Bravo AF: 0.0771

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		0.13
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: rs11744339; hg19: chr5-145978081;