rs2857766

Variant names:

• chr6-29666226-G-C
• rs2857766
• NM_206809.4:c.511G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_206809.4(MOG):​c.511G>C​(p.Val171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,610,262 control chromosomes in the GnomAD database, including 40,265 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (3156 hom., cov: 31)
  • Exomes 𝑓: 0.22 (37109 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.303
• Publications: 46 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008852869).
• BP6: Variant 6-29666226-G-C is Benign according to our data. Variant chr6-29666226-G-C is described in ClinVar as Benign. ClinVar VariationId is 3059372.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.511G>C	p.Val171Leu	missense_variant	Exon 3 of 8	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.511G>C	p.Val171Leu	missense_variant	Exon 3 of 8	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29517 AN: 151918 Hom.: 3155 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.222 AC: 54792 AN: 246528 AF XY: 0.216

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.290

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.220 AC: 320474 AN: 1458228 Hom.: 37109 Cov.: 32 AF XY: 0.217 AC XY: 157182 AN XY: 725530

African (AFR) AF: 0.107 AC: 3570 AN: 33450

American (AMR) AF: 0.238 AC: 10645 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4076 AN: 26126

East Asian (EAS) AF: 0.265 AC: 10533 AN: 39686

South Asian (SAS) AF: 0.104 AC: 8993 AN: 86230

European-Finnish (FIN) AF: 0.301 AC: 15758 AN: 52298

Middle Eastern (MID) AF: 0.126 AC: 728 AN: 5762

European-Non Finnish (NFE) AF: 0.229 AC: 254013 AN: 1109630

Other (OTH) AF: 0.202 AC: 12158 AN: 60324

GnomAD4 genome AF: 0.194 AC: 29520 AN: 152034 Hom.: 3156 Cov.: 31 AF XY: 0.195 AC XY: 14464 AN XY: 74302

African (AFR) AF: 0.116 AC: 4789 AN: 41462

American (AMR) AF: 0.183 AC: 2798 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1405 AN: 5160

South Asian (SAS) AF: 0.111 AC: 534 AN: 4818

European-Finnish (FIN) AF: 0.292 AC: 3083 AN: 10560

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

European-Non Finnish (NFE) AF: 0.232 AC: 15751 AN: 67980

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.222 Hom.: 2973

Bravo AF: 0.186

TwinsUK AF: 0.232 AC: 861

ALSPAC AF: 0.242 AC: 934

ESP6500AA AF: 0.122 AC: 368

ESP6500EA AF: 0.228 AC: 1233

ExAC AF: 0.220 AC: 26034

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MOG-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.8
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.70	T;T;T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0089	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;L;L;.;.;L;L;L;L;L
PhyloP100		0.30
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.53	N;N;N;N;D;N;N;N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0040	B;B;.;B;B;.;.;B;B;P;B
Vest4		0.14
MPC		0.24
ClinPred		0.0040	T
GERP RS		0.63
Varity_R		0.054
gMVP		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2857766; hg19: chr6-29634003;