rs2252711

Variant names:

• chr6-29658544-T-C
• rs2252711
• NM_206809.4:c.89-775T>C

Variant summary

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

The NM_206809.4(MOG):​c.89-775T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,946 control chromosomes in the GnomAD database, including 3,242 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 0.20 (3242 hom., cov: 32)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 25 publications found

Genes affected

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MOG Gene-Disease associations (from GenCC):

• narcolepsy 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	NM_206809.4	MANE Select	c.89-775T>C		intron	N/A	NP_996532.2
	MOG	NM_001363610.2		c.89-775T>C		intron	N/A	NP_001350539.1
	MOG	NM_002433.5		c.89-775T>C		intron	N/A	NP_002424.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	ENST00000376917.8	TSL:1 MANE Select	c.89-775T>C		intron	N/A	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.89-775T>C		intron	N/A	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.89-775T>C		intron	N/A	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29825 AN: 151828 Hom.: 3241 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.196 AC: 29829 AN: 151946 Hom.: 3242 Cov.: 32 AF XY: 0.197 AC XY: 14627 AN XY: 74266

African (AFR) AF: 0.116 AC: 4789 AN: 41410

American (AMR) AF: 0.200 AC: 3054 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1417 AN: 5176

South Asian (SAS) AF: 0.112 AC: 538 AN: 4810

European-Finnish (FIN) AF: 0.293 AC: 3088 AN: 10556

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15779 AN: 67952

Other (OTH) AF: 0.161 AC: 339 AN: 2108

Alfa AF: 0.220 Hom.: 13041

Bravo AF: 0.189

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.59
PhyloP100		-0.51
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: rs2252711; hg19: chr6-29626321;