NM_002717.4:c.472A>G

Variant names:

• chr8-26360986-A-G
• NM_002717.4:c.472A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002717.4(PPP2R2A):​c.472A>G​(p.Arg158Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R2A NM_002717.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 0 publications found

Genes affected

PPP2R2A (HGNC:9304): (protein phosphatase 2 regulatory subunit Balpha) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 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 an alpha isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27952182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002717.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	NM_002717.4	MANE Select	c.472A>G	p.Arg158Gly	missense	Exon 6 of 10	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.502A>G	p.Arg168Gly	missense	Exon 6 of 10	NP_001171062.1	P63151-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	ENST00000380737.8	TSL:1 MANE Select	c.472A>G	p.Arg158Gly	missense	Exon 6 of 10	ENSP00000370113.3	P63151-1
	PPP2R2A	ENST00000660435.1		c.-6A>G		5_prime_UTR_premature_start_codon_gain	Exon 7 of 11	ENSP00000499441.1	A0A590UJJ1
	PPP2R2A	ENST00000521557.5	TSL:4	c.-6A>G		5_prime_UTR_premature_start_codon_gain	Exon 6 of 6	ENSP00000428165.1	E5RJV1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720178

African (AFR) AF: 0.00 AC: 0 AN: 32608

American (AMR) AF: 0.00 AC: 0 AN: 39584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 38974

South Asian (SAS) AF: 0.00 AC: 0 AN: 82736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109120

Other (OTH) AF: 0.00 AC: 0 AN: 59814

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0045
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.2
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.14
Sift	Benign	0.21	T
Sift4G	Benign	0.26	T
Polyphen		0.044	B
Vest4		0.48
MutPred		0.51		Loss of stability (P = 0.0443)
MVP		0.70
MPC		1.4
ClinPred		0.85	D
GERP RS		4.2
Varity_R		0.15
gMVP		0.83
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

hg19: chr8-26218502;