8-30812403-T-C

Variant names:

• chr8-30812403-T-C
• rs1218747654
• NM_001009552.2:c.19A>G

Variant summary

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

The NM_001009552.2(PPP2CB):​c.19A>G​(p.Thr7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PPP2CB NM_001009552.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74

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=0.09060395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2CB	NM_001009552.2	c.19A>G	p.Thr7Ala	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.19A>G	p.Thr7Ala	missense_variant	Exon 1 of 7	1	NM_001009552.2	ENSP00000221138.4
PPP2CB	ENST00000518564.1	c.19A>G	p.Thr7Ala	missense_variant	Exon 1 of 3	3		ENSP00000428142.1
PPP2CB	ENST00000518243.5	c.68+383A>G		intron_variant	Intron 1 of 4	3		ENSP00000428618.1
PPP2CB	ENST00000520500.1	n.428+1484A>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000247

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19A>G (p.T7A) alteration is located in exon 1 (coding exon 1) of the PPP2CB gene. This alteration results from a A to G substitution at nucleotide position 19, causing the threonine (T) at amino acid position 7 to be replaced by an alanine (A). 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	0.061
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.058
Sift	Benign	0.42	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.21		Loss of phosphorylation at T7 (P = 0.0395);Loss of phosphorylation at T7 (P = 0.0395);
MVP		0.33
MPC		0.78
ClinPred		0.067	T
GERP RS		2.1
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.085
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1218747654; hg19: chr8-30669919;