2-216006757-C-T

Variant names:

• chr2-216006757-C-T
• rs3770564
• NM_018000.3:c.95+6476G>A

Variant summary

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

The NM_018000.3(MREG):​c.95+6476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,270 control chromosomes in the GnomAD database, including 54,692 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 0.85 (54692 hom., cov: 33)
• Consequence: MREG NM_018000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MREG	NM_018000.3	c.95+6476G>A		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.95+6476G>A		intron_variant	Intron 1 of 4	2	NM_018000.3	ENSP00000263268.6

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128903 AN: 152152 Hom.: 54643 Cov.: 33

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.847 AC: 129010 AN: 152270 Hom.: 54692 Cov.: 33 AF XY: 0.848 AC XY: 63095 AN XY: 74446

African (AFR) AF: 0.844 AC: 35050 AN: 41552

American (AMR) AF: 0.871 AC: 13318 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3208 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4990 AN: 5190

South Asian (SAS) AF: 0.850 AC: 4108 AN: 4832

European-Finnish (FIN) AF: 0.815 AC: 8631 AN: 10594

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56880 AN: 68014

Other (OTH) AF: 0.857 AC: 1813 AN: 2116

Alfa AF: 0.844 Hom.: 111307

Bravo AF: 0.853

Asia WGS AF: 0.891 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		-0.33
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: rs3770564; hg19: chr2-216871480;