rs11934638

Variant names:

• chr4-75898346-C-T
• rs11934638
• NM_006239.3:c.-58-1963G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPEF2	NM_006239.3	c.-58-1963G>A		intron_variant	Intron 1 of 16	ENST00000286719.12	NP_006230.2
PPEF2	XM_011532039.3	c.-2021G>A		5_prime_UTR_variant	Exon 1 of 16		XP_011530341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF2	ENST00000286719.12	c.-58-1963G>A		intron_variant	Intron 1 of 16	1	NM_006239.3	ENSP00000286719.6
PPEF2	ENST00000511880.7	n.-79-1942G>A		intron_variant	Intron 1 of 17	1		ENSP00000426186.2
PPEF2	ENST00000510607.1	n.343-1942G>A		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.155 AC: 6420 AN: 41520

American (AMR) AF: 0.168 AC: 2564 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3470

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5184

South Asian (SAS) AF: 0.142 AC: 685 AN: 4826

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18720 AN: 67992

Other (OTH) AF: 0.216 AC: 455 AN: 2110

Alfa AF: 0.254 Hom.: 2952

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
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs11934638; hg19: chr4-76819499;