8-26370083-A-G

Variant names:

• chr8-26370083-A-G
• rs3824232
• NM_002717.4:c.1065-51A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002717.4(PPP2R2A):​c.1065-51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.1065-51A>G		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.1095-51A>G		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.1065-51A>G		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000315985.7	TSL:2	c.1095-51A>G		intron	N/A	ENSP00000325074.7
	PPP2R2A	ENST00000665949.1		c.744-51A>G		intron	N/A	ENSP00000499648.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406364 Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1 AN XY: 695860

African (AFR) AF: 0.00 AC: 0 AN: 31400

American (AMR) AF: 0.00 AC: 0 AN: 39364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24518

East Asian (EAS) AF: 0.00 AC: 0 AN: 38952

South Asian (SAS) AF: 0.00 AC: 0 AN: 81018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075402

Other (OTH) AF: 0.00 AC: 0 AN: 57852

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		-0.71

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: rs3824232; hg19: chr8-26227599;