rs2535248

Variant names:

• chr6-29667150-A-G
• rs2535248
• NM_206809.4:c.551-493A>G

Variant summary

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

The NM_206809.4(MOG):​c.551-493A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,242 control chromosomes in the GnomAD database, including 733 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 0.072 (733 hom., cov: 32)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.551-493A>G		intron_variant	Intron 3 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.551-493A>G		intron_variant	Intron 3 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10901 AN: 152124 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0788

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0717 AC: 10916 AN: 152242 Hom.: 733 Cov.: 32 AF XY: 0.0682 AC XY: 5081 AN XY: 74452

African (AFR) AF: 0.171 AC: 7105 AN: 41518

American (AMR) AF: 0.0753 AC: 1151 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 273 AN: 3466

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4826

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10622

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0308 AC: 2098 AN: 68020

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.0431 Hom.: 577

Bravo AF: 0.0835

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.043
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: rs2535248; hg19: chr6-29634927;