rs2535262

Variant names:

• chr6-29660456-G-A
• rs2535262
• NM_206809.4:c.436+790G>A

Variant summary

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

The NM_206809.4(MOG):​c.436+790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 148,110 control chromosomes in the GnomAD database, including 2,479 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 0.17 (2479 hom., cov: 24)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 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.436+790G>A		intron	N/A	NP_996532.2
	MOG	NM_001363610.2		c.436+790G>A		intron	N/A	NP_001350539.1
	MOG	NM_002433.5		c.436+790G>A		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.436+790G>A		intron	N/A	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.436+790G>A		intron	N/A	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.436+790G>A		intron	N/A	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 25554 AN: 148000 Hom.: 2476 Cov.: 24

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.173 AC: 25577 AN: 148110 Hom.: 2479 Cov.: 24 AF XY: 0.170 AC XY: 12228 AN XY: 71992

African (AFR) AF: 0.164 AC: 6573 AN: 40148

American (AMR) AF: 0.241 AC: 3538 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1113 AN: 3454

East Asian (EAS) AF: 0.0419 AC: 207 AN: 4944

South Asian (SAS) AF: 0.133 AC: 603 AN: 4542

European-Finnish (FIN) AF: 0.106 AC: 1039 AN: 9838

Middle Eastern (MID) AF: 0.184 AC: 53 AN: 288

European-Non Finnish (NFE) AF: 0.177 AC: 11908 AN: 67296

Other (OTH) AF: 0.203 AC: 408 AN: 2014

Alfa AF: 0.173 Hom.: 315

Bravo AF: 0.184

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-0.20
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: rs2535262; hg19: chr6-29628233;