11-64927887-C-G

Variant names:

• chr11-64927887-C-G
• NM_006244.4:c.482C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006244.4(PPP2R5B):​c.482C>G​(p.Ser161Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPP2R5B NM_006244.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5B	NM_006244.4	c.482C>G	p.Ser161Trp	missense_variant	Exon 4 of 14	ENST00000164133.7	NP_006235.1
PPP2R5B	XM_047427199.1	c.482C>G	p.Ser161Trp	missense_variant	Exon 3 of 13		XP_047283155.1
PPP2R5B	XM_011545132.3	c.395C>G	p.Ser132Trp	missense_variant	Exon 5 of 15		XP_011543434.1
PPP2R5B	XM_047427200.1	c.395C>G	p.Ser132Trp	missense_variant	Exon 5 of 15		XP_047283156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5B	ENST00000164133.7	c.482C>G	p.Ser161Trp	missense_variant	Exon 4 of 14	1	NM_006244.4	ENSP00000164133.2
PPP2R5B	ENST00000526559.5	c.482C>G	p.Ser161Trp	missense_variant	Exon 4 of 5	5		ENSP00000437088.1
PPP2R5B	ENST00000532850.1	c.224C>G	p.Ser75Trp	missense_variant	Exon 4 of 5	3		ENSP00000436136.1
PPP2R5B	ENST00000528530.1	n.154C>G		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455630 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724488

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D;D;D
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	3.3	.;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.61
MutPred		0.54		Gain of catalytic residue at S161 (P = 0);Gain of catalytic residue at S161 (P = 0);.;
MVP		0.51
MPC		2.5
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.82
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr11-64695359;