8-30812367-C-T

Variant names:

• chr8-30812367-C-T
• rs759127793
• NM_001009552.2:c.55G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009552.2(PPP2CB):​c.55G>A​(p.Glu19Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,413,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PPP2CB NM_001009552.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54

Genes affected

PPP2CB (HGNC:9300): (protein phosphatase 2 catalytic subunit beta) This gene encodes the phosphatase 2A catalytic subunit. 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. This gene encodes a beta isoform of the catalytic subunit. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20141125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2CB	NM_001009552.2	c.55G>A	p.Glu19Lys	missense_variant	Exon 1 of 7	ENST00000221138.9	NP_001009552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2CB	ENST00000221138.9	c.55G>A	p.Glu19Lys	missense_variant	Exon 1 of 7	1	NM_001009552.2	ENSP00000221138.4
PPP2CB	ENST00000518564.1	c.55G>A	p.Glu19Lys	missense_variant	Exon 1 of 3	3		ENSP00000428142.1
PPP2CB	ENST00000518243.5	c.68+419G>A		intron_variant	Intron 1 of 4	3		ENSP00000428618.1
PPP2CB	ENST00000520500.1	n.428+1520G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1413116 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703556

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: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.55G>A (p.E19K) alteration is located in exon 1 (coding exon 1) of the PPP2CB gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glutamic acid (E) at amino acid position 19 to be replaced by a lysine (K). 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	0.32
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.19
Sift	Benign	0.32	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.38
MutPred		0.34		Gain of methylation at E19 (P = 0.0036);Gain of methylation at E19 (P = 0.0036);
MVP		0.48
MPC		0.89
ClinPred		0.55	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs759127793; hg19: chr8-30669883;