Genetic Variant PPEF2:n.*585A>G (chr4-75881917-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000511880.7(PPEF2):n.*585A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,298 control chromosomes in the GnomAD database, including 546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.051 ( 546 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PPEF2
ENST00000511880.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.210

Publications

0 publications found

Variant links:

Genes affected

PPEF2 (HGNC:9244): (protein phosphatase with EF-hand domain 2) This gene encodes a member of the serine/threonine protein phosphatase with EF-hand motif family. The protein contains a protein phosphatase catalytic domain, and at least two EF-hand calcium-binding motifs in its C terminus. Although its substrate(s) is unknown, the encoded protein, which is expressed specifically in photoreceptors and the pineal, has been suggested to play a role in the visual system. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. [provided by RefSeq, Jul 2008]

PPEF2 links:

ENSG00000300740 (HGNC:):

ENSG00000300740 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPEF2	NM_006239.3 link	c.933+1009A>G	intron_variant	Intron 10 of 16	ENST00000286719.12	NP_006230.2	O14830-1
PPEF2	XM_011532039.3 link	c.933+1009A>G	intron_variant	Intron 9 of 15		XP_011530341.1	O14830-1
LOC105377285	XR_938895.3 link	n.399+3142T>C	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPEF2	ENST00000511880.7 link	n.*585A>G	non_coding_transcript_exon_variant	Exon 11 of 18	1		ENSP00000426186.2	E7EPQ9
PPEF2	ENST00000511880.7 link	n.*585A>G	3_prime_UTR_variant	Exon 11 of 18	1		ENSP00000426186.2	E7EPQ9
PPEF2	ENST00000286719.12 link	c.933+1009A>G	intron_variant	Intron 10 of 16	1	NM_006239.3	ENSP00000286719.6	O14830-1
ENSG00000300740	ENST00000773743.1 link	n.262+3142T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

7761

AN:

152180

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00409

Gnomad OTH

AF:

0.0492

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0512

AC:

7797

AN:

152298

Hom.:

546

Cov.:

AF XY:

0.0496

AC XY:

3695

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.160

AC:

6658

AN:

41538

American (AMR)

AF:

0.0385

AC:

588

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

124

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00409

AC:

278

AN:

68028

Other (OTH)

AF:

0.0487

AC:

103

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

344

688

1032

1376

1720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0165

Hom.:

Bravo

AF:

0.0579

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over