5-146878727-AGCTGCTGCTGCTGCTGCTGCTGCT-AGCTGCT

Variant names:

• chr5-146878727-AGCTGCTGCTGCTGCTGCT-A
• rs10591869
• NM_181675.4:c.-279_-262delAGCAGCAGCAGCAGCAGC

Variant summary

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

The NM_181675.4(PPP2R2B):​c.-279_-262delAGCAGCAGCAGCAGCAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,297,602 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PPP2R2B NM_181675.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter U:1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

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

• BP6: Variant 5-146878727-AGCTGCTGCTGCTGCTGCT-A is Benign according to our data. Variant chr5-146878727-AGCTGCTGCTGCTGCTGCT-A is described in ClinVar as Benign. ClinVar VariationId is 1050601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181675.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2B	NM_181675.4	MANE Select	c.-279_-262delAGCAGCAGCAGCAGCAGC		5_prime_UTR	Exon 1 of 10	NP_858061.3	Q00005-1
	PPP2R2B	NM_001428277.1		c.-674_-657delAGCAGCAGCAGCAGCAGC		5_prime_UTR	Exon 1 of 9	NP_001415206.1	Q00005-1
	PPP2R2B	NM_001428279.1		c.-169_-152delAGCAGCAGCAGCAGCAGC		5_prime_UTR	Exon 1 of 10	NP_001415208.1	Q00005-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2B	ENST00000394411.9	TSL:2 MANE Select	c.-279_-262delAGCAGCAGCAGCAGCAGC		5_prime_UTR	Exon 1 of 10	ENSP00000377933.3	Q00005-1
	PPP2R2B	ENST00000453001.5	TSL:1	c.-792_-775delAGCAGCAGCAGCAGCAGC		5_prime_UTR	Exon 1 of 10	ENSP00000398779.2	Q00005-6
	PPP2R2B	ENST00000394414.5	TSL:1	c.75-550_75-533delAGCAGCAGCAGCAGCAGC		intron	N/A	ENSP00000377936.1	Q00005-5

Frequencies

GnomAD3 genomes AF: 0.000153 AC: 23 AN: 150488 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000813

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 192 AN: 1146996 Hom.: 0 AF XY: 0.000169 AC XY: 95 AN XY: 562102

African (AFR) AF: 0.00 AC: 0 AN: 23470

American (AMR) AF: 0.00 AC: 0 AN: 27150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15242

East Asian (EAS) AF: 0.000126 AC: 3 AN: 23798

South Asian (SAS) AF: 0.000317 AC: 23 AN: 72534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15564

Middle Eastern (MID) AF: 0.000351 AC: 1 AN: 2848

European-Non Finnish (NFE) AF: 0.000173 AC: 160 AN: 923476

Other (OTH) AF: 0.000117 AC: 5 AN: 42914

GnomAD4 genome AF: 0.000153 AC: 23 AN: 150606 Hom.: 0 Cov.: 0 AF XY: 0.000163 AC XY: 12 AN XY: 73474

African (AFR) AF: 0.0000732 AC: 3 AN: 41004

American (AMR) AF: 0.00 AC: 0 AN: 15176

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

East Asian (EAS) AF: 0.000815 AC: 4 AN: 4910

South Asian (SAS) AF: 0.00106 AC: 5 AN: 4700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000163 AC: 11 AN: 67634

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 47

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=290/10	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;