2-216002218-C-G

Variant names:

• chr2-216002218-C-G
• rs3770562
• NM_018000.3:c.96-5753G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018000.3(MREG):​c.96-5753G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,034 control chromosomes in the GnomAD database, including 23,739 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 0.55 (23739 hom., cov: 32)
• Consequence: MREG NM_018000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MREG	NM_018000.3	c.96-5753G>C		intron_variant	Intron 1 of 4	ENST00000263268.11	NP_060470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MREG	ENST00000263268.11	c.96-5753G>C		intron_variant	Intron 1 of 4	2	NM_018000.3	ENSP00000263268.6

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84274 AN: 151916 Hom.: 23717 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.555 AC: 84352 AN: 152034 Hom.: 23739 Cov.: 32 AF XY: 0.557 AC XY: 41428 AN XY: 74322

African (AFR) AF: 0.631 AC: 26188 AN: 41484

American (AMR) AF: 0.575 AC: 8793 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3464

East Asian (EAS) AF: 0.671 AC: 3473 AN: 5176

South Asian (SAS) AF: 0.485 AC: 2326 AN: 4800

European-Finnish (FIN) AF: 0.574 AC: 6067 AN: 10572

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34418 AN: 67922

Other (OTH) AF: 0.495 AC: 1044 AN: 2110

Alfa AF: 0.391 Hom.: 1031

Bravo AF: 0.560

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.48
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: rs3770562; hg19: chr2-216866941;