2-215996315-TTT-GCG

Variant names:

• chr2-215996315-TTT-GCG
• NM_018000.3:c.244_246delAAAinsCGC
• MREG p.Lys82Arg

Variant summary

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

The NM_018000.3(MREG):​c.244_246delAAAinsCGC​(p.Lys82Arg) 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: MREG NM_018000.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

MREG (HGNC:25478): (melanoregulin) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in melanocyte differentiation; melanosome transport; and phagosome maturation. Predicted to act upstream of or within developmental pigmentation. Predicted to be located in late endosome membrane and melanosome membrane. Predicted to be intrinsic component of organelle membrane. Predicted to be part of protein-containing complex. Predicted to be active in melanosome. [provided by Alliance of Genome Resources, Apr 2022]

PECR (HGNC:18281): (peroxisomal trans-2-enoyl-CoA reductase) Enables signaling receptor binding activity and trans-2-enoyl-CoA reductase (NADPH) activity. Involved in phytol metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

PECR Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018000.3. 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
	MREG	NM_018000.3	MANE Select	c.244_246delAAAinsCGC	p.Lys82Arg	missense	N/A	NP_060470.2	Q8N565-1
	MREG	NM_001372188.1		c.244_246delAAAinsCGC	p.Lys82Arg	missense	N/A	NP_001359117.1
	MREG	NM_001372189.1		c.82_84delAAAinsCGC	p.Lys28Arg	missense	N/A	NP_001359118.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MREG	ENST00000263268.11	TSL:2 MANE Select	c.244_246delAAAinsCGC	p.Lys82Arg	missense	N/A	ENSP00000263268.6	Q8N565-1
	MREG	ENST00000439791.5	TSL:4	c.82_84delAAAinsCGC	p.Lys28Arg	missense	N/A	ENSP00000411076.1	C9JAG4
	MREG	ENST00000424992.5	TSL:5	c.82_84delAAAinsCGC	p.Lys28Arg	missense	N/A	ENSP00000413302.1	C9JYV9

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		3.1

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: chr2-216861038;