chr8-26360759-A-T

Variant names:

• chr8-26360759-A-T
• rs17309529
• NM_002717.4:c.460-215A>T

Variant summary

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

The NM_001177591.2(PPP2R2A):​c.490-215A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 488,364 control chromosomes in the GnomAD database, including 822 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 0.045 (190 hom., cov: 32)
  • Exomes 𝑓: 0.051 (632 hom.)
• Consequence: PPP2R2A NM_001177591.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 3 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=-0.84).
• 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_001177591.2. 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.460-215A>T		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.490-215A>T		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.460-215A>T		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000315985.7	TSL:2	c.490-215A>T		intron	N/A	ENSP00000325074.7
	PPP2R2A	ENST00000919755.1		c.460-215A>T		intron	N/A	ENSP00000589814.1

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6872 AN: 152204 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0513 AC: 17236 AN: 336042 Hom.: 632 Cov.: 4 AF XY: 0.0539 AC XY: 9396 AN XY: 174314

African (AFR) AF: 0.0292 AC: 228 AN: 7800

American (AMR) AF: 0.0204 AC: 187 AN: 9150

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 1295 AN: 11102

East Asian (EAS) AF: 0.000305 AC: 7 AN: 22948

South Asian (SAS) AF: 0.114 AC: 2450 AN: 21538

European-Finnish (FIN) AF: 0.0659 AC: 1647 AN: 24984

Middle Eastern (MID) AF: 0.0608 AC: 98 AN: 1612

European-Non Finnish (NFE) AF: 0.0475 AC: 10263 AN: 216116

Other (OTH) AF: 0.0510 AC: 1061 AN: 20792

GnomAD4 genome AF: 0.0452 AC: 6884 AN: 152322 Hom.: 190 Cov.: 32 AF XY: 0.0475 AC XY: 3534 AN XY: 74478

African (AFR) AF: 0.0301 AC: 1253 AN: 41578

American (AMR) AF: 0.0282 AC: 431 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.123 AC: 592 AN: 4830

European-Finnish (FIN) AF: 0.0671 AC: 712 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0492 AC: 3349 AN: 68024

Other (OTH) AF: 0.0345 AC: 73 AN: 2114

Alfa AF: 0.0475 Hom.: 17

Bravo AF: 0.0384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		0.28
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: rs17309529; hg19: chr8-26218275;