8-26363084-T-C

Variant names:

• chr8-26363084-T-C
• rs17309613
• NM_002717.4:c.802+236T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002717.4(PPP2R2A):​c.802+236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 397,138 control chromosomes in the GnomAD database, including 747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.039 (177 hom., cov: 31)
  • Exomes 𝑓: 0.054 (570 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	NM_002717.4	MANE Select	c.802+236T>C		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.832+236T>C		intron	N/A	NP_001171062.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	ENST00000380737.8	TSL:1 MANE Select	c.802+236T>C		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000517754.1	TSL:2	n.463T>C		non_coding_transcript_exon	Exon 2 of 4
	PPP2R2A	ENST00000315985.7	TSL:2	c.832+236T>C		intron	N/A	ENSP00000325074.7

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5977 AN: 152056 Hom.: 178 Cov.: 31

Gnomad AFR AF: 0.00947

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0536 AC: 13142 AN: 244964 Hom.: 570 Cov.: 4 AF XY: 0.0584 AC XY: 7429 AN XY: 127304

African (AFR) AF: 0.00821 AC: 62 AN: 7552

American (AMR) AF: 0.0239 AC: 207 AN: 8646

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 969 AN: 8368

East Asian (EAS) AF: 0.000343 AC: 6 AN: 17514

South Asian (SAS) AF: 0.137 AC: 2757 AN: 20186

European-Finnish (FIN) AF: 0.0673 AC: 935 AN: 13888

Middle Eastern (MID) AF: 0.0646 AC: 77 AN: 1192

European-Non Finnish (NFE) AF: 0.0481 AC: 7339 AN: 152624

Other (OTH) AF: 0.0527 AC: 790 AN: 14994

GnomAD4 genome AF: 0.0393 AC: 5976 AN: 152174 Hom.: 177 Cov.: 31 AF XY: 0.0415 AC XY: 3089 AN XY: 74404

African (AFR) AF: 0.00944 AC: 392 AN: 41526

American (AMR) AF: 0.0258 AC: 394 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.122 AC: 587 AN: 4818

European-Finnish (FIN) AF: 0.0677 AC: 717 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3349 AN: 67980

Other (OTH) AF: 0.0294 AC: 62 AN: 2112

Alfa AF: 0.0516 Hom.: 123

Bravo AF: 0.0319

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.61
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs17309613; hg19: chr8-26220600;