NM_002717.4:c.459+59A>C

Variant names:

• chr8-26360340-A-C
• rs17309515
• NM_002717.4:c.459+59A>C

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.459+59A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 965,884 control chromosomes in the GnomAD database, including 1,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (194 hom., cov: 32)
  • Exomes 𝑓: 0.053 (1658 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.302
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-26360340-A-C is Benign according to our data. Variant chr8-26360340-A-C is described in ClinVar as [Benign]. Clinvar id is 1679064.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.459+59A>C		intron_variant	Intron 5 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.459+59A>C		intron_variant	Intron 5 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6876 AN: 152166 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0532 AC: 43276 AN: 813600 Hom.: 1658 AF XY: 0.0566 AC XY: 23972 AN XY: 423872

African (AFR) AF: 0.0276 AC: 537 AN: 19474

American (AMR) AF: 0.0216 AC: 647 AN: 29982

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 2236 AN: 18476

East Asian (EAS) AF: 0.000195 AC: 7 AN: 35912

South Asian (SAS) AF: 0.127 AC: 7686 AN: 60318

European-Finnish (FIN) AF: 0.0690 AC: 3240 AN: 46976

Middle Eastern (MID) AF: 0.0693 AC: 281 AN: 4052

European-Non Finnish (NFE) AF: 0.0473 AC: 26535 AN: 560406

Other (OTH) AF: 0.0554 AC: 2107 AN: 38004

GnomAD4 genome AF: 0.0452 AC: 6888 AN: 152284 Hom.: 194 Cov.: 32 AF XY: 0.0475 AC XY: 3537 AN XY: 74466

African (AFR) AF: 0.0300 AC: 1248 AN: 41554

American (AMR) AF: 0.0282 AC: 432 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.122 AC: 591 AN: 4830

European-Finnish (FIN) AF: 0.0679 AC: 720 AN: 10606

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0493 AC: 3351 AN: 68020

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0453 Hom.: 65

Bravo AF: 0.0384

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Hereditary breast ovarian cancer syndrome Benign:1

Apr 19, 2022

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

Significance: 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	2.1
DANN	Benign	0.57
PhyloP100		-0.30
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: rs17309515; hg19: chr8-26217856;