4-75872030-CC-TT

Variant names:

• chr4-75872030-CC-TT
• NM_006239.3:c.1643_1644delGGinsAA
• PPEF2 p.Arg548Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006239.3(PPEF2):​c.1643_1644delGGinsAA​(p.Arg548Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPEF2 NM_006239.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006239.3. 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
	PPEF2	NM_006239.3	MANE Select	c.1643_1644delGGinsAA	p.Arg548Lys	missense	N/A	NP_006230.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPEF2	ENST00000286719.12	TSL:1 MANE Select	c.1643_1644delGGinsAA	p.Arg548Lys	missense	N/A	ENSP00000286719.6	O14830-1
	PPEF2	ENST00000511880.7	TSL:1	n.*1881_*1882delGGinsAA		non_coding_transcript_exon	Exon 14 of 18	ENSP00000426186.2	E7EPQ9
	PPEF2	ENST00000511880.7	TSL:1	n.*1881_*1882delGGinsAA		3_prime_UTR	Exon 14 of 18	ENSP00000426186.2	E7EPQ9

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-76793183;