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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4	c.802+78A>G		intron_variant	Intron 7 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.802+78A>G		intron_variant	Intron 7 of 9	1	NM_002717.4	ENSP00000370113.3

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

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary breast ovarian cancer syndrome Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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;