rs34629706

Variant names:

• chr3-136002194-C-T
• rs34629706
• NM_002718.5:c.696C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002718.5(PPP2R3A):​c.696C>T​(p.Cys232Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,613,220 control chromosomes in the GnomAD database, including 5,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.060 (405 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4880 hom.)
• Consequence: PPP2R3A NM_002718.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.221
• Publications: 5 publications found

Genes affected

PPP2R3A (HGNC:9307): (protein phosphatase 2 regulatory subunit B''alpha) This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 3-136002194-C-T is Benign according to our data. Variant chr3-136002194-C-T is described in ClinVar as Benign. ClinVar VariationId is 3038187.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.221 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002718.5. 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
	PPP2R3A	NM_002718.5	MANE Select	c.696C>T	p.Cys232Cys	synonymous	Exon 2 of 14	NP_002709.2
	PPP2R3A	NM_001190447.2		c.-213-24638C>T		intron	N/A	NP_001177376.1	Q06190-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R3A	ENST00000264977.8	TSL:1 MANE Select	c.696C>T	p.Cys232Cys	synonymous	Exon 2 of 14	ENSP00000264977.3	Q06190-1
	PPP2R3A	ENST00000872859.1		c.696C>T	p.Cys232Cys	synonymous	Exon 2 of 14	ENSP00000542918.1
	PPP2R3A	ENST00000872860.1		c.696C>T	p.Cys232Cys	synonymous	Exon 2 of 14	ENSP00000542919.1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9183 AN: 152020 Hom.: 404 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0773

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0664 AC: 16455 AN: 247968 AF XY: 0.0691

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.0219

Gnomad ASJ exome AF: 0.0448

Gnomad EAS exome AF: 0.000654

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.0810

Gnomad OTH exome AF: 0.0656

GnomAD4 exome AF: 0.0753 AC: 110048 AN: 1461082 Hom.: 4880 Cov.: 39 AF XY: 0.0758 AC XY: 55126 AN XY: 726872

African (AFR) AF: 0.0111 AC: 370 AN: 33408

American (AMR) AF: 0.0228 AC: 1017 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.0443 AC: 1157 AN: 26110

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39684

South Asian (SAS) AF: 0.0759 AC: 6538 AN: 86142

European-Finnish (FIN) AF: 0.159 AC: 8452 AN: 53302

Middle Eastern (MID) AF: 0.0392 AC: 226 AN: 5768

European-Non Finnish (NFE) AF: 0.0794 AC: 88262 AN: 1111676

Other (OTH) AF: 0.0665 AC: 4013 AN: 60358

GnomAD4 genome AF: 0.0603 AC: 9178 AN: 152138 Hom.: 405 Cov.: 32 AF XY: 0.0634 AC XY: 4715 AN XY: 74354

African (AFR) AF: 0.0128 AC: 533 AN: 41530

American (AMR) AF: 0.0303 AC: 463 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0772 AC: 372 AN: 4820

European-Finnish (FIN) AF: 0.167 AC: 1761 AN: 10550

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0838 AC: 5698 AN: 67972

Other (OTH) AF: 0.0478 AC: 101 AN: 2112

Alfa AF: 0.0613 Hom.: 430

Bravo AF: 0.0460

Asia WGS AF: 0.0220 AC: 77 AN: 3478

EpiCase AF: 0.0717

EpiControl AF: 0.0681

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPP2R3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.1
DANN	Benign	0.60
PhyloP100		-0.22
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: rs34629706; hg19: chr3-135721036; COSMIC: COSV53859583;