NM_006246.5:c.1008A>G

Variant names:

• chr14-63389678-T-C
• rs61756432
• NM_006246.5:c.1008A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006246.5(PPP2R5E):​c.1008A>G​(p.Gln336Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,612,280 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (15 hom., cov: 32)
  • Exomes 𝑓: 0.014 (173 hom.)
• Consequence: PPP2R5E NM_006246.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770
• Publications: 3 publications found

Genes affected

PPP2R5E (HGNC:9313): (protein phosphatase 2 regulatory subunit B'epsilon) The protein encoded by this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A 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 epsilon isoform of the regulatory subunit B56 subfamily. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 14-63389678-T-C is Benign according to our data. Variant chr14-63389678-T-C is described in ClinVar as Benign. ClinVar VariationId is 769862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.077 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0138 (20138/1460000) while in subpopulation NFE AF = 0.0158 (17551/1111312). AF 95% confidence interval is 0.0156. There are 173 homozygotes in GnomAdExome4. There are 9797 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1396 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006246.5. 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
	PPP2R5E	NM_006246.5	MANE Select	c.1008A>G	p.Gln336Gln	synonymous	Exon 11 of 14	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.1008A>G	p.Gln336Gln	synonymous	Exon 11 of 14	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.1008A>G	p.Gln336Gln	synonymous	Exon 11 of 14	NP_001269109.1	Q16537-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.1008A>G	p.Gln336Gln	synonymous	Exon 11 of 14	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.1008A>G	p.Gln336Gln	synonymous	Exon 11 of 14	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.1394A>G		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes AF: 0.00917 AC: 1396 AN: 152162 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00962

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.00767

GnomAD2 exomes AF: 0.00881 AC: 2196 AN: 249178 AF XY: 0.00911

Gnomad AFR exome AF: 0.00290

Gnomad AMR exome AF: 0.00536

Gnomad ASJ exome AF: 0.0193

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00916

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.00775

GnomAD4 exome AF: 0.0138 AC: 20138 AN: 1460000 Hom.: 173 Cov.: 30 AF XY: 0.0135 AC XY: 9797 AN XY: 726196

African (AFR) AF: 0.00203 AC: 68 AN: 33432

American (AMR) AF: 0.00601 AC: 267 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 511 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39606

South Asian (SAS) AF: 0.00626 AC: 537 AN: 85764

European-Finnish (FIN) AF: 0.00807 AC: 431 AN: 53388

Middle Eastern (MID) AF: 0.000891 AC: 5 AN: 5612

European-Non Finnish (NFE) AF: 0.0158 AC: 17551 AN: 1111312

Other (OTH) AF: 0.0127 AC: 767 AN: 60332

GnomAD4 genome AF: 0.00917 AC: 1396 AN: 152280 Hom.: 15 Cov.: 32 AF XY: 0.00885 AC XY: 659 AN XY: 74460

African (AFR) AF: 0.00289 AC: 120 AN: 41552

American (AMR) AF: 0.00706 AC: 108 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4824

European-Finnish (FIN) AF: 0.00962 AC: 102 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 940 AN: 68026

Other (OTH) AF: 0.00759 AC: 16 AN: 2108

Alfa AF: 0.0116 Hom.: 6

Bravo AF: 0.00857

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0119

EpiControl AF: 0.0127

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		-0.077
Mutation Taster		=91/9	polymorphism

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: rs61756432; hg19: chr14-63856396; COSMIC: COSV61741925;