chr14-63415211-G-T

Variant names:

• chr14-63415211-G-T
• rs10133826
• NM_006246.5:c.478C>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_006246.5(PPP2R5E):​c.478C>A​(p.Arg160Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00258 in 1,601,366 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (48 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (34 hom.)
• Consequence: PPP2R5E NM_006246.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.13
• Publications: 1 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 14-63415211-G-T is Benign according to our data. Variant chr14-63415211-G-T is described in ClinVar as Benign. ClinVar VariationId is 786620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1941/151942) while in subpopulation AFR AF = 0.0431 (1783/41388). AF 95% confidence interval is 0.0414. There are 48 homozygotes in GnomAd4. There are 940 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1941 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.478C>A	p.Arg160Arg	synonymous	Exon 5 of 14	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.478C>A	p.Arg160Arg	synonymous	Exon 5 of 14	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.478C>A	p.Arg160Arg	synonymous	Exon 5 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.478C>A	p.Arg160Arg	synonymous	Exon 5 of 14	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.478C>A	p.Arg160Arg	synonymous	Exon 5 of 14	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.864C>A		non_coding_transcript_exon	Exon 4 of 12

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1936 AN: 151824 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00361 AC: 903 AN: 250026 AF XY: 0.00264

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00377

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000433

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00151 AC: 2192 AN: 1449424 Hom.: 34 Cov.: 29 AF XY: 0.00138 AC XY: 999 AN XY: 721722

African (AFR) AF: 0.0420 AC: 1388 AN: 33086

American (AMR) AF: 0.00382 AC: 170 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 46 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.0000468 AC: 4 AN: 85456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00437 AC: 25 AN: 5726

European-Non Finnish (NFE) AF: 0.000312 AC: 344 AN: 1102084

Other (OTH) AF: 0.00359 AC: 215 AN: 59968

GnomAD4 genome AF: 0.0128 AC: 1941 AN: 151942 Hom.: 48 Cov.: 32 AF XY: 0.0127 AC XY: 940 AN XY: 74284

African (AFR) AF: 0.0431 AC: 1783 AN: 41388

American (AMR) AF: 0.00517 AC: 79 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67958

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00454 Hom.: 18

Bravo AF: 0.0147

Asia WGS AF: 0.00202 AC: 7 AN: 3476

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	-0.37
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10133826; hg19: chr14-63881929;