8-26367442-G-T

Variant names:

• chr8-26367442-G-T
• rs7823021
• NM_002717.4:c.1064+1036G>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.1064+1036G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,172 control chromosomes in the GnomAD database, including 40,491 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 0.73 (40491 hom., cov: 33)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 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.1064+1036G>T		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.1094+1036G>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.1064+1036G>T		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000315985.7	TSL:2	c.1094+1036G>T		intron	N/A	ENSP00000325074.7
	PPP2R2A	ENST00000665949.1		c.743+1036G>T		intron	N/A	ENSP00000499648.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110535 AN: 152054 Hom.: 40440 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.727 AC: 110640 AN: 152172 Hom.: 40491 Cov.: 33 AF XY: 0.731 AC XY: 54342 AN XY: 74384

African (AFR) AF: 0.760 AC: 31564 AN: 41530

American (AMR) AF: 0.652 AC: 9958 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3468

East Asian (EAS) AF: 0.877 AC: 4544 AN: 5180

South Asian (SAS) AF: 0.756 AC: 3647 AN: 4824

European-Finnish (FIN) AF: 0.788 AC: 8344 AN: 10594

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48249 AN: 67982

Other (OTH) AF: 0.714 AC: 1509 AN: 2114

Alfa AF: 0.700 Hom.: 21413

Bravo AF: 0.715

Asia WGS AF: 0.792 AC: 2752 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.15
PhyloP100		-0.34
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: rs7823021; hg19: chr8-26224958;