rs2535253

Variant names:

• chr6-29665242-C-A
• rs2535253
• NM_206809.4:c.437-910C>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.437-910C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,598 control chromosomes in the GnomAD database, including 28,924 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 0.61 (28924 hom., cov: 29)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 6 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.437-910C>A		intron_variant	Intron 2 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.437-910C>A		intron_variant	Intron 2 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92366 AN: 151482 Hom.: 28881 Cov.: 29

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.610 AC: 92465 AN: 151598 Hom.: 28924 Cov.: 29 AF XY: 0.606 AC XY: 44853 AN XY: 74038

African (AFR) AF: 0.721 AC: 29803 AN: 41316

American (AMR) AF: 0.658 AC: 10024 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2301 AN: 3462

East Asian (EAS) AF: 0.580 AC: 2961 AN: 5108

South Asian (SAS) AF: 0.706 AC: 3391 AN: 4800

European-Finnish (FIN) AF: 0.363 AC: 3803 AN: 10480

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.562 AC: 38144 AN: 67890

Other (OTH) AF: 0.651 AC: 1372 AN: 2108

Alfa AF: 0.578 Hom.: 3194

Bravo AF: 0.635

Asia WGS AF: 0.671 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.048
DANN	Benign	0.19
PhyloP100		-0.84
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: rs2535253; hg19: chr6-29633019;