11-64925843-C-A

Variant names:

• chr11-64925843-C-A
• rs753530198
• NM_006244.4:c.109C>A

Variant summary

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

The NM_006244.4(PPP2R5B):​c.109C>A​(p.Arg37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PPP2R5B NM_006244.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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.109C>A	p.Arg37Ser	missense_variant	Exon 2 of 14	ENST00000164133.7	NP_006235.1
PPP2R5B	XM_047427199.1	c.109C>A	p.Arg37Ser	missense_variant	Exon 1 of 13		XP_047283155.1
PPP2R5B	XM_011545132.3	c.27-5C>A		splice_region_variant, intron_variant	Intron 2 of 14		XP_011543434.1
PPP2R5B	XM_047427200.1	c.27-5C>A		splice_region_variant, intron_variant	Intron 2 of 14		XP_047283156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5B	ENST00000164133.7	c.109C>A	p.Arg37Ser	missense_variant	Exon 2 of 14	1	NM_006244.4	ENSP00000164133.2
PPP2R5B	ENST00000526559.5	c.109C>A	p.Arg37Ser	missense_variant	Exon 2 of 5	5		ENSP00000437088.1
PPP2R5B	ENST00000532850.1	c.-145-5C>A		splice_region_variant, intron_variant	Intron 1 of 4	3		ENSP00000436136.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.37
Sift	Benign	0.17	T;T
Sift4G	Benign	0.88	T;T
Polyphen		1.0	.;D
Vest4		0.56
MutPred		0.27		Gain of phosphorylation at R37 (P = 4e-04);Gain of phosphorylation at R37 (P = 4e-04);
MVP		0.30
MPC		0.31
ClinPred		0.89	D
GERP RS		3.3
Varity_R		0.26
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs753530198; hg19: chr11-64693315;