rs2535245

Variant names:

• chr6-29669045-T-C
• rs2535245
• NM_206809.4:c.592+1121T>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.592+1121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,160 control chromosomes in the GnomAD database, including 3,118 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 0.19 (3118 hom., cov: 30)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.592+1121T>C		intron_variant	Intron 5 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.592+1121T>C		intron_variant	Intron 5 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29195 AN: 151042 Hom.: 3111 Cov.: 30

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.193 AC: 29232 AN: 151160 Hom.: 3118 Cov.: 30 AF XY: 0.190 AC XY: 14049 AN XY: 73852

African (AFR) AF: 0.202 AC: 8325 AN: 41162

American (AMR) AF: 0.285 AC: 4311 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1294 AN: 3464

East Asian (EAS) AF: 0.0465 AC: 237 AN: 5096

South Asian (SAS) AF: 0.123 AC: 587 AN: 4774

European-Finnish (FIN) AF: 0.112 AC: 1171 AN: 10470

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12616 AN: 67772

Other (OTH) AF: 0.236 AC: 492 AN: 2088

Alfa AF: 0.185 Hom.: 341

Bravo AF: 0.208

Asia WGS AF: 0.105 AC: 366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.34
PhyloP100		-1.9
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: rs2535245; hg19: chr6-29636822;