11-64925806-A-C

Position:

• chr11-64925806-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006244.4(PPP2R5B):​c.72A>C​(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R5B NM_006244.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.431

Genes affected

PPP2R5B (HGNC:9310): (protein phosphatase 2 regulatory subunit B'beta) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A 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 B56 subfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-64925806-A-C is Benign according to our data. Variant chr11-64925806-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3388194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.431 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R5B	NM_006244.4	c.72A>C	p.Pro24Pro	synonymous_variant	2/14	ENST00000164133.7	NP_006235.1
PPP2R5B	XM_047427199.1	c.72A>C	p.Pro24Pro	synonymous_variant	1/13		XP_047283155.1
PPP2R5B	XM_011545132.3	c.27-42A>C		intron_variant			XP_011543434.1
PPP2R5B	XM_047427200.1	c.27-42A>C		intron_variant			XP_047283156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5B	ENST00000164133.7	c.72A>C	p.Pro24Pro	synonymous_variant	2/14	1	NM_006244.4	ENSP00000164133.2
PPP2R5B	ENST00000526559.5	c.72A>C	p.Pro24Pro	synonymous_variant	2/5	5		ENSP00000437088.1
PPP2R5B	ENST00000532850.1	c.-145-42A>C		intron_variant		3		ENSP00000436136.1

Frequencies

GnomAD3 genomes AF: 0.000814 AC: 63 AN: 77412 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000925

Gnomad AMI AF: 0.00644

Gnomad AMR AF: 0.000528

Gnomad ASJ AF: 0.000486

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00205

Gnomad FIN AF: 0.000240

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000789

Gnomad OTH AF: 0.00189

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000474 AC: 550 AN: 1160970 Hom.: 0 Cov.: 34 AF XY: 0.000485 AC XY: 277 AN XY: 571156

Gnomad4 AFR exome AF: 0.000336

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.000655

Gnomad4 EAS exome AF: 0.00159

Gnomad4 SAS exome AF: 0.000769

Gnomad4 FIN exome AF: 0.00276

Gnomad4 NFE exome AF: 0.000314

Gnomad4 OTH exome AF: 0.000747

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000814 AC: 63 AN: 77418 Hom.: 0 Cov.: 24 AF XY: 0.000583 AC XY: 22 AN XY: 37762

Gnomad4 AFR AF: 0.000923

Gnomad4 AMR AF: 0.000528

Gnomad4 ASJ AF: 0.000486

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00206

Gnomad4 FIN AF: 0.000240

Gnomad4 NFE AF: 0.000789

Gnomad4 OTH AF: 0.00187

Alfa AF: 0.0148 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

PPP2R5B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.3
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1024487131; hg19: chr11-64693278; COSMIC: COSV51209915; COSMIC: COSV51209915;