chr8-26354736-G-A

Variant names:

• chr8-26354736-G-A
• rs3779915
• NM_002717.4:c.346+103G>A

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.346+103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 991,490 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: 0.0000020 (0 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 0 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=-0.85).

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.346+103G>A		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.376+103G>A		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.346+103G>A		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000315985.7	TSL:2	c.376+103G>A		intron	N/A	ENSP00000325074.7
	PPP2R2A	ENST00000665949.1		c.-97+103G>A		intron	N/A	ENSP00000499648.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000202 AC: 2 AN: 991490 Hom.: 0 AF XY: 0.00000207 AC XY: 1 AN XY: 482972

African (AFR) AF: 0.00 AC: 0 AN: 21610

American (AMR) AF: 0.00 AC: 0 AN: 17524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14876

East Asian (EAS) AF: 0.00 AC: 0 AN: 30602

South Asian (SAS) AF: 0.00 AC: 0 AN: 27104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2954

European-Non Finnish (NFE) AF: 0.00000250 AC: 2 AN: 800542

Other (OTH) AF: 0.00 AC: 0 AN: 41160

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		0.0050

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: rs3779915; hg19: chr8-26212252;