rs3808565

Variant names:

• chr8-26370124-A-G
• rs3808565
• NM_002717.4:c.1065-10A>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.1065-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,611,178 control chromosomes in the GnomAD database, including 7,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (910 hom., cov: 32)
  • Exomes 𝑓: 0.059 (6358 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Scores: Splicing: ADA: 0.00001008
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.85
• Publications: 11 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=-0.9).
• BP6: Variant 8-26370124-A-G is Benign according to our data. Variant chr8-26370124-A-G is described in ClinVar as Benign. ClinVar VariationId is 1679073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 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.1065-10A>G		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.1095-10A>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.1065-10A>G		intron	N/A	ENSP00000370113.3	P63151-1
	PPP2R2A	ENST00000315985.7	TSL:2	c.1095-10A>G		intron	N/A	ENSP00000325074.7	P63151-2
	PPP2R2A	ENST00000919755.1		c.987-10A>G		intron	N/A	ENSP00000589814.1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11820 AN: 151978 Hom.: 909 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0696

GnomAD2 exomes AF: 0.0863 AC: 21593 AN: 250316 AF XY: 0.0826

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0693

Gnomad ASJ exome AF: 0.0577

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.0792

Gnomad NFE exome AF: 0.0417

Gnomad OTH exome AF: 0.0608

GnomAD4 exome AF: 0.0592 AC: 86359 AN: 1459080 Hom.: 6358 Cov.: 31 AF XY: 0.0592 AC XY: 42982 AN XY: 725568

African (AFR) AF: 0.105 AC: 3518 AN: 33404

American (AMR) AF: 0.0662 AC: 2955 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 1514 AN: 26108

East Asian (EAS) AF: 0.464 AC: 18368 AN: 39626

South Asian (SAS) AF: 0.0811 AC: 6985 AN: 86104

European-Finnish (FIN) AF: 0.0781 AC: 4163 AN: 53310

Middle Eastern (MID) AF: 0.0335 AC: 193 AN: 5762

European-Non Finnish (NFE) AF: 0.0401 AC: 44480 AN: 1109854

Other (OTH) AF: 0.0694 AC: 4183 AN: 60284

GnomAD4 genome AF: 0.0777 AC: 11825 AN: 152098 Hom.: 910 Cov.: 32 AF XY: 0.0806 AC XY: 5998 AN XY: 74386

African (AFR) AF: 0.102 AC: 4239 AN: 41474

American (AMR) AF: 0.0502 AC: 767 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2233 AN: 5138

South Asian (SAS) AF: 0.0986 AC: 476 AN: 4830

European-Finnish (FIN) AF: 0.0842 AC: 892 AN: 10590

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2827 AN: 67994

Other (OTH) AF: 0.0712 AC: 150 AN: 2106

Alfa AF: 0.0574 Hom.: 1369

Bravo AF: 0.0781

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.22
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000010
dbscSNV1_RF	Benign	0.0
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: rs3808565; hg19: chr8-26227640; COSMIC: COSV60098344;