8-26354736-G-C

Variant names:

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

Variant summary

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

The NM_002717.4(PPP2R2A):​c.346+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,143,566 control chromosomes in the GnomAD database, including 1,158 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 0.027 (250 hom., cov: 32)
  • Exomes 𝑓: 0.017 (908 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 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.346+103G>C		intron	N/A	NP_002708.1
	PPP2R2A	NM_001177591.2		c.376+103G>C		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>C		intron	N/A	ENSP00000370113.3
	PPP2R2A	ENST00000315985.7	TSL:2	c.376+103G>C		intron	N/A	ENSP00000325074.7
	PPP2R2A	ENST00000665949.1		c.-97+103G>C		intron	N/A	ENSP00000499648.1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 152104 Hom.: 244 Cov.: 32

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00950

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0168 AC: 16644 AN: 991344 Hom.: 908 AF XY: 0.0168 AC XY: 8096 AN XY: 482898

African (AFR) AF: 0.00301 AC: 65 AN: 21610

American (AMR) AF: 0.228 AC: 3991 AN: 17488

Ashkenazi Jewish (ASJ) AF: 0.00773 AC: 115 AN: 14876

East Asian (EAS) AF: 0.121 AC: 3695 AN: 30592

South Asian (SAS) AF: 0.0741 AC: 2008 AN: 27084

European-Finnish (FIN) AF: 0.00857 AC: 301 AN: 35116

Middle Eastern (MID) AF: 0.00609 AC: 18 AN: 2954

European-Non Finnish (NFE) AF: 0.00690 AC: 5521 AN: 800472

Other (OTH) AF: 0.0226 AC: 930 AN: 41152

GnomAD4 genome AF: 0.0270 AC: 4115 AN: 152222 Hom.: 250 Cov.: 32 AF XY: 0.0300 AC XY: 2231 AN XY: 74428

African (AFR) AF: 0.00597 AC: 248 AN: 41540

American (AMR) AF: 0.136 AC: 2072 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.117 AC: 605 AN: 5180

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4826

European-Finnish (FIN) AF: 0.00669 AC: 71 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00950 AC: 646 AN: 68002

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0221 Hom.: 22

Bravo AF: 0.0363

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		0.0050
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: rs3779915; hg19: chr8-26212252; COSMIC: COSV60099311; COSMIC: COSV60099311;