2-216033935-G-A

Position:

• chr2-216033935-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372189.1(MREG):​c.-68+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,104 control chromosomes in the GnomAD database, including 40,053 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 0.72 (40052 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: MREG NM_001372189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MREG	NM_001372189.1	c.-68+27C>T		intron_variant			NP_001359118.1
PECR	XR_001738847.3	n.1065-1083C>T		intron_variant
PECR	XR_007078552.1	n.1065-1083C>T		intron_variant
PECR	XR_007078553.1	n.1065-1083C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MREG	ENST00000424992.5	c.-68+27C>T		intron_variant		5		ENSP00000413302.1
PECR	ENST00000442122.5	n.*440+5256C>T		intron_variant		2		ENSP00000395512.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110055 AN: 151984 Hom.: 40006 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.724 AC: 110157 AN: 152102 Hom.: 40052 Cov.: 32 AF XY: 0.724 AC XY: 53830 AN XY: 74334

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.696

Alfa AF: 0.698 Hom.: 57184

Bravo AF: 0.731

Asia WGS AF: 0.668 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7590720; hg19: chr2-216898658;