5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant names:

• chr5-146878727-A-AGCTGCT
• rs10591869
• ENST00000530902.5:n.162_167dupAGCAGC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000530902.5(PPP2R2B):​n.162_167dupAGCAGC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (19 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R2B ENST00000530902.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.19
• 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)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 5-146878727-A-AGCTGCT is Benign according to our data. Variant chr5-146878727-A-AGCTGCT is described in ClinVar as [Benign]. Clinvar id is 2655888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 180 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2B	NM_181675.4	c.-267_-262dupAGCAGC		5_prime_UTR_variant	Exon 1 of 10	ENST00000394411.9	NP_858061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2B	ENST00000394411.9	c.-267_-262dupAGCAGC		5_prime_UTR_variant	Exon 1 of 10	2	NM_181675.4	ENSP00000377933.3

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 174 AN: 150470 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000610

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000562

Gnomad OTH AF: 0.000484

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00215 AC: 2437 AN: 1134968 Hom.: 19 Cov.: 27 AF XY: 0.00276 AC XY: 1536 AN XY: 555826

African (AFR) AF: 0.00256 AC: 59 AN: 23076

American (AMR) AF: 0.00394 AC: 104 AN: 26414

Ashkenazi Jewish (ASJ) AF: 0.00357 AC: 53 AN: 14828

East Asian (EAS) AF: 0.00215 AC: 50 AN: 23308

South Asian (SAS) AF: 0.0162 AC: 1140 AN: 70494

European-Finnish (FIN) AF: 0.00149 AC: 23 AN: 15468

Middle Eastern (MID) AF: 0.00535 AC: 15 AN: 2806

European-Non Finnish (NFE) AF: 0.000980 AC: 898 AN: 916300

Other (OTH) AF: 0.00225 AC: 95 AN: 42274

GnomAD4 genome AF: 0.00120 AC: 180 AN: 150588 Hom.: 0 Cov.: 0 AF XY: 0.00154 AC XY: 113 AN XY: 73466

African (AFR) AF: 0.00156 AC: 64 AN: 41004

American (AMR) AF: 0.000659 AC: 10 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000611 AC: 3 AN: 4910

South Asian (SAS) AF: 0.0134 AC: 63 AN: 4698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000562 AC: 38 AN: 67624

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 47

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PPP2R2B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=284/16	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10591869; hg19: chr5-146258290;