NM_002544.5:c.62G>A

Variant names:

• chr17-31296270-C-T
• rs11080149
• NM_002544.5:c.62G>A
• OMG p.Gly21Asp

Variant summary

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

The NM_002544.5(OMG):​c.62G>A​(p.Gly21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,850 control chromosomes in the GnomAD database, including 12,075 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.081 (686 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11389 hom.)
• Consequence: OMG NM_002544.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.45
• Publications: 43 publications found

Genes affected

OMG (HGNC:8135): (oligodendrocyte myelin glycoprotein) Predicted to enable identical protein binding activity. Predicted to be involved in neuron projection regeneration. Predicted to act upstream of or within regulation of collateral sprouting of intact axon in response to injury. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 Gene-Disease associations (from GenCC):

• neurofibromatosis type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• neurofibromatosis-Noonan syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• Moyamoya disease

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014791489).
• BP6: Variant 17-31296270-C-T is Benign according to our data. Variant chr17-31296270-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055468.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002544.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OMG	NM_002544.5	MANE Select	c.62G>A	p.Gly21Asp	missense	Exon 2 of 2	NP_002535.3
	NF1	NM_001042492.3	MANE Select	c.4836-29550C>T		intron	N/A	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.4773-29550C>T		intron	N/A	NP_000258.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OMG	ENST00000247271.5	TSL:1 MANE Select	c.62G>A	p.Gly21Asp	missense	Exon 2 of 2	ENSP00000247271.4	P23515
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.4836-29550C>T		intron	N/A	ENSP00000351015.4	P21359-1
	NF1	ENST00000356175.7	TSL:1	c.4773-29550C>T		intron	N/A	ENSP00000348498.3	P21359-2

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12354 AN: 152084 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0708

GnomAD2 exomes AF: 0.0912 AC: 22893 AN: 251078 AF XY: 0.0909

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.0821

Gnomad ASJ exome AF: 0.0660

Gnomad EAS exome AF: 0.000925

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.0875

GnomAD4 exome AF: 0.118 AC: 172364 AN: 1461648 Hom.: 11389 Cov.: 32 AF XY: 0.115 AC XY: 83976 AN XY: 727156

African (AFR) AF: 0.0207 AC: 694 AN: 33474

American (AMR) AF: 0.0811 AC: 3628 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1767 AN: 26132

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39692

South Asian (SAS) AF: 0.0428 AC: 3691 AN: 86252

European-Finnish (FIN) AF: 0.105 AC: 5623 AN: 53414

Middle Eastern (MID) AF: 0.0392 AC: 226 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 150739 AN: 1111812

Other (OTH) AF: 0.0989 AC: 5971 AN: 60384

GnomAD4 genome AF: 0.0812 AC: 12352 AN: 152202 Hom.: 686 Cov.: 32 AF XY: 0.0803 AC XY: 5974 AN XY: 74410

African (AFR) AF: 0.0245 AC: 1020 AN: 41548

American (AMR) AF: 0.0766 AC: 1171 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4824

European-Finnish (FIN) AF: 0.0943 AC: 998 AN: 10584

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8488 AN: 67992

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.107 Hom.: 3405

Bravo AF: 0.0775

Asia WGS AF: 0.0160 AC: 61 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.118

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	OMG-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.035
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.42	T
Varity_R		0.14
gMVP		0.37
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11080149;

hg19: chr17-29623288;

COSMIC: COSV55988007;