NM_002717.4:c.181-5907C>T

Variant names:

• chr8-26348561-C-T
• rs1594829
• NM_002717.4:c.181-5907C>T

Variant summary

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

The NM_002717.4(PPP2R2A):​c.181-5907C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,150 control chromosomes in the GnomAD database, including 3,486 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 0.21 (3486 hom., cov: 33)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	NM_002717.4	MANE Select	c.181-5907C>T		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.211-5907C>T		intron	N/A	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.181-5907C>T		intron	N/A	ENSP00000370113.3	P63151-1
	PPP2R2A	ENST00000315985.7	TSL:2	c.211-5907C>T		intron	N/A	ENSP00000325074.7	P63151-2
	PPP2R2A	ENST00000919755.1		c.181-5907C>T		intron	N/A	ENSP00000589814.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31276 AN: 152032 Hom.: 3483 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31280 AN: 152150 Hom.: 3486 Cov.: 33 AF XY: 0.199 AC XY: 14821 AN XY: 74374

African (AFR) AF: 0.221 AC: 9190 AN: 41502

American (AMR) AF: 0.171 AC: 2616 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.139 AC: 670 AN: 4826

European-Finnish (FIN) AF: 0.154 AC: 1626 AN: 10576

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15291 AN: 67994

Other (OTH) AF: 0.216 AC: 456 AN: 2116

Alfa AF: 0.217 Hom.: 10708

Bravo AF: 0.208

Asia WGS AF: 0.0820 AC: 283 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.50
DANN	Benign	0.26
PhyloP100		-1.4
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: rs1594829; hg19: chr8-26206077;