chr8-26354481-C-T

Variant names:

• chr8-26354481-C-T
• rs1207739648
• NM_002717.4:c.194C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002717.4(PPP2R2A):​c.194C>T​(p.Ser65Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PPP2R2A NM_002717.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15216032).

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.194C>T	p.Ser65Phe	missense	Exon 4 of 10	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.224C>T	p.Ser75Phe	missense	Exon 4 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.194C>T	p.Ser65Phe	missense	Exon 4 of 10	ENSP00000370113.3	P63151-1
	PPP2R2A	ENST00000315985.7	TSL:2	c.224C>T	p.Ser75Phe	missense	Exon 4 of 10	ENSP00000325074.7	P63151-2
	PPP2R2A	ENST00000919755.1		c.194C>T	p.Ser65Phe	missense	Exon 4 of 10	ENSP00000589814.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000443 AC: 1 AN: 225926 AF XY: 0.00000815

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000371

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397406 Hom.: 0 Cov.: 30 AF XY: 0.00000433 AC XY: 3 AN XY: 692856

African (AFR) AF: 0.00 AC: 0 AN: 31406

American (AMR) AF: 0.0000269 AC: 1 AN: 37160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23808

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.00 AC: 0 AN: 74170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5526

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077942

Other (OTH) AF: 0.00 AC: 0 AN: 57202

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	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.51
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PhyloP100		2.7
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.054
Sift	Benign	0.036	D
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.38		Loss of disorder (P = 0.0091)
MVP		0.31
MPC		1.3
ClinPred		0.26	T
GERP RS		6.0
Varity_R		0.14
gMVP		0.35
Mutation Taster		=47/53	disease causing

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

dbSNP: rs1207739648; hg19: chr8-26211997;