chr8-26370083-A-C

Variant names:

• chr8-26370083-A-C
• rs3824232
• NM_002717.4:c.1065-51A>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.1065-51A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,557,578 control chromosomes in the GnomAD database, including 21,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3207 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18009 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.712
• 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=-0.81).
• BP6: Variant 8-26370083-A-C is Benign according to our data. Variant chr8-26370083-A-C is described in ClinVar as Benign. ClinVar VariationId is 1679072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4	c.1065-51A>C		intron_variant	Intron 9 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.1065-51A>C		intron_variant	Intron 9 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28336 AN: 152000 Hom.: 3207 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.168 AC: 38415 AN: 228572 AF XY: 0.163

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.423

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.148 AC: 207801 AN: 1405458 Hom.: 18009 Cov.: 29 AF XY: 0.147 AC XY: 102362 AN XY: 695402

African (AFR) AF: 0.289 AC: 9057 AN: 31366

American (AMR) AF: 0.128 AC: 5034 AN: 39354

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3330 AN: 24506

East Asian (EAS) AF: 0.464 AC: 18066 AN: 38936

South Asian (SAS) AF: 0.144 AC: 11639 AN: 80994

European-Finnish (FIN) AF: 0.122 AC: 6402 AN: 52392

Middle Eastern (MID) AF: 0.159 AC: 866 AN: 5456

European-Non Finnish (NFE) AF: 0.134 AC: 144384 AN: 1074628

Other (OTH) AF: 0.156 AC: 9023 AN: 57826

GnomAD4 genome AF: 0.186 AC: 28354 AN: 152120 Hom.: 3207 Cov.: 32 AF XY: 0.186 AC XY: 13821 AN XY: 74360

African (AFR) AF: 0.285 AC: 11838 AN: 41488

American (AMR) AF: 0.135 AC: 2069 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2245 AN: 5146

South Asian (SAS) AF: 0.164 AC: 792 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10578

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9099 AN: 68020

Other (OTH) AF: 0.181 AC: 381 AN: 2108

Alfa AF: 0.156 Hom.: 466

Bravo AF: 0.191

Asia WGS AF: 0.276 AC: 959 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-0.71
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: rs3824232; hg19: chr8-26227599; COSMIC: COSV60098826;