11-64926835-A-G

Variant names:

• chr11-64926835-A-G
• NM_006244.4:c.323A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006244.4(PPP2R5B):​c.323A>G​(p.Asn108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PPP2R5B NM_006244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5B	NM_006244.4	c.323A>G	p.Asn108Ser	missense_variant	Exon 3 of 14	ENST00000164133.7	NP_006235.1
PPP2R5B	XM_047427199.1	c.323A>G	p.Asn108Ser	missense_variant	Exon 2 of 13		XP_047283155.1
PPP2R5B	XM_011545132.3	c.236A>G	p.Asn79Ser	missense_variant	Exon 4 of 15		XP_011543434.1
PPP2R5B	XM_047427200.1	c.236A>G	p.Asn79Ser	missense_variant	Exon 4 of 15		XP_047283156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5B	ENST00000164133.7	c.323A>G	p.Asn108Ser	missense_variant	Exon 3 of 14	1	NM_006244.4	ENSP00000164133.2
PPP2R5B	ENST00000526559.5	c.323A>G	p.Asn108Ser	missense_variant	Exon 3 of 5	5		ENSP00000437088.1
PPP2R5B	ENST00000532850.1	c.65A>G	p.Asn22Ser	missense_variant	Exon 3 of 5	3		ENSP00000436136.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.323A>G (p.N108S) alteration is located in exon 3 (coding exon 2) of the PPP2R5B gene. This alteration results from a A to G substitution at nucleotide position 323, causing the asparagine (N) at amino acid position 108 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D;D;D
Eigen	Benign	0.014
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.10
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.11	.;B;.
Vest4		0.63
MutPred		0.48		Gain of disorder (P = 0.0696);Gain of disorder (P = 0.0696);.;
MVP		0.55
MPC		1.9
ClinPred		0.95	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64694307;