rs11934638

chr4-75898346-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006239.3(PPEF2):c.-58-1963G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,186 control chromosomes in the GnomAD database, including 4,056 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 0.22 (4056 hom., cov: 33)
• Consequence: PPEF2 NM_006239.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPEF2	NM_006239.3	c.-58-1963G>A		intron_variant		ENST00000286719.12
PPEF2	XM_011532039.3	c.-2021G>A		5_prime_UTR_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPEF2	ENST00000286719.12	c.-58-1963G>A		intron_variant		1	NM_006239.3	P1
PPEF2	ENST00000511880.7	c.-79-1942G>A		intron_variant, NMD_transcript_variant		1
PPEF2	ENST00000510607.1	n.343-1942G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33213 AN: 152068 Hom.: 4056 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33216 AN: 152186 Hom.: 4056 Cov.: 33 AF XY: 0.216 AC XY: 16039 AN XY: 74392

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.216

Alfa AF: 0.254 Hom.: 2681

Bravo AF: 0.206

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs11934638; hg19: chr4-76819499;