14-63384503-G-A

Variant names:

• chr14-63384503-G-A
• rs61732995
• NM_006246.5:c.1143C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006246.5(PPP2R5E):​c.1143C>T​(p.Asn381Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,613,792 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (42 hom.)
• Consequence: PPP2R5E NM_006246.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0600
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 14-63384503-G-A is Benign according to our data. Variant chr14-63384503-G-A is described in ClinVar as Benign. ClinVar VariationId is 768658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2147/152164) while in subpopulation AFR AF = 0.0491 (2036/41492). AF 95% confidence interval is 0.0473. There are 53 homozygotes in GnomAd4. There are 1030 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2147 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.1143C>T	p.Asn381Asn	synonymous	Exon 12 of 14	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.1143C>T	p.Asn381Asn	synonymous	Exon 12 of 14	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.1143C>T	p.Asn381Asn	synonymous	Exon 12 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.1143C>T	p.Asn381Asn	synonymous	Exon 12 of 14	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.1143C>T	p.Asn381Asn	synonymous	Exon 12 of 14	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.1529C>T		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2139 AN: 152046 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00357 AC: 897 AN: 251336 AF XY: 0.00271

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00137 AC: 2004 AN: 1461628 Hom.: 42 Cov.: 30 AF XY: 0.00114 AC XY: 826 AN XY: 727138

African (AFR) AF: 0.0486 AC: 1625 AN: 33460

American (AMR) AF: 0.00271 AC: 121 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5752

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1111852

Other (OTH) AF: 0.00285 AC: 172 AN: 60384

GnomAD4 genome AF: 0.0141 AC: 2147 AN: 152164 Hom.: 53 Cov.: 32 AF XY: 0.0138 AC XY: 1030 AN XY: 74420

African (AFR) AF: 0.0491 AC: 2036 AN: 41492

American (AMR) AF: 0.00497 AC: 76 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68002

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00784 Hom.: 15

Bravo AF: 0.0157

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	-0.41
CADD	Benign	8.2
DANN	Benign	0.65
PhyloP100		0.060
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs61732995; hg19: chr14-63851221;