rs17309592

Variant names:

• chr8-26362926-A-G
• rs17309592
• NM_002717.4:c.802+78A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002717.4(PPP2R2A):​c.802+78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,392,080 control chromosomes in the GnomAD database, including 2,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (174 hom., cov: 31)
  • Exomes 𝑓: 0.053 (2300 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-26362926-A-G is Benign according to our data. Variant chr8-26362926-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1679066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 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.802+78A>G		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.832+78A>G		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.802+78A>G		intron	N/A	ENSP00000370113.3	P63151-1
	PPP2R2A	ENST00000315985.7	TSL:2	c.832+78A>G		intron	N/A	ENSP00000325074.7	P63151-2
	PPP2R2A	ENST00000919755.1		c.724+78A>G		intron	N/A	ENSP00000589814.1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5981 AN: 152180 Hom.: 175 Cov.: 31

Gnomad AFR AF: 0.00924

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0531 AC: 65840 AN: 1239782 Hom.: 2300 Cov.: 17 AF XY: 0.0562 AC XY: 34878 AN XY: 620108

African (AFR) AF: 0.00770 AC: 219 AN: 28428

American (AMR) AF: 0.0209 AC: 733 AN: 35056

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2893 AN: 24136

East Asian (EAS) AF: 0.000275 AC: 10 AN: 36428

South Asian (SAS) AF: 0.128 AC: 9845 AN: 77150

European-Finnish (FIN) AF: 0.0686 AC: 2697 AN: 39310

Middle Eastern (MID) AF: 0.0694 AC: 306 AN: 4412

European-Non Finnish (NFE) AF: 0.0491 AC: 46216 AN: 942092

Other (OTH) AF: 0.0554 AC: 2921 AN: 52770

GnomAD4 genome AF: 0.0393 AC: 5980 AN: 152298 Hom.: 174 Cov.: 31 AF XY: 0.0415 AC XY: 3088 AN XY: 74468

African (AFR) AF: 0.00922 AC: 383 AN: 41562

American (AMR) AF: 0.0258 AC: 395 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.122 AC: 589 AN: 4820

European-Finnish (FIN) AF: 0.0679 AC: 721 AN: 10618

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3356 AN: 68022

Other (OTH) AF: 0.0293 AC: 62 AN: 2114

Alfa AF: 0.0444 Hom.: 27

Bravo AF: 0.0319

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs17309592; hg19: chr8-26220442;