rs762178

Variant names:

• chr21-33027093-A-G
• rs762178
• NM_005806.4:c.231A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005806.4(OLIG2):​c.231A>G​(p.Ser77Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,609,692 control chromosomes in the GnomAD database, including 248,745 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 0.53 (21735 hom., cov: 32)
  • Exomes 𝑓: 0.55 (227010 hom.)
• Consequence: OLIG2 NM_005806.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 29 publications found

Genes affected

OLIG2 (HGNC:9398): (oligodendrocyte transcription factor 2) This gene encodes a basic helix-loop-helix transcription factor which is expressed in oligodendroglial tumors of the brain. The protein is an essential regulator of ventral neuroectodermal progenitor cell fate. The gene is involved in a chromosomal translocation t(14;21)(q11.2;q22) associated with T-cell acute lymphoblastic leukemia. Its chromosomal location is within a region of chromosome 21 which has been suggested to play a role in learning deficits associated with Down syndrome. [provided by RefSeq, Jul 2008]

ENSG00000227757 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005806.4. 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
	OLIG2	NM_005806.4	MANE Select	c.231A>G	p.Ser77Ser	synonymous	Exon 2 of 2	NP_005797.1	Q13516

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLIG2	ENST00000382357.4	TSL:1 MANE Select	c.231A>G	p.Ser77Ser	synonymous	Exon 2 of 2	ENSP00000371794.3	Q13516
	OLIG2	ENST00000333337.3	TSL:6	c.231A>G	p.Ser77Ser	synonymous	Exon 1 of 1	ENSP00000331040.3	Q13516
	OLIG2	ENST00000877220.1		c.231A>G	p.Ser77Ser	synonymous	Exon 2 of 2	ENSP00000547279.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80503 AN: 151850 Hom.: 21734 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.527

GnomAD2 exomes AF: 0.511 AC: 123283 AN: 241414 AF XY: 0.514

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.488

Gnomad ASJ exome AF: 0.628

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.531

Gnomad NFE exome AF: 0.568

Gnomad OTH exome AF: 0.537

GnomAD4 exome AF: 0.553 AC: 806143 AN: 1457724 Hom.: 227010 Cov.: 80 AF XY: 0.552 AC XY: 400090 AN XY: 724854

African (AFR) AF: 0.518 AC: 17324 AN: 33414

American (AMR) AF: 0.493 AC: 21762 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 16395 AN: 25994

East Asian (EAS) AF: 0.188 AC: 7439 AN: 39602

South Asian (SAS) AF: 0.472 AC: 40471 AN: 85674

European-Finnish (FIN) AF: 0.528 AC: 27839 AN: 52738

Middle Eastern (MID) AF: 0.547 AC: 3151 AN: 5760

European-Non Finnish (NFE) AF: 0.576 AC: 639638 AN: 1110188

Other (OTH) AF: 0.533 AC: 32124 AN: 60214

GnomAD4 genome AF: 0.530 AC: 80527 AN: 151968 Hom.: 21735 Cov.: 32 AF XY: 0.525 AC XY: 38963 AN XY: 74268

African (AFR) AF: 0.523 AC: 21679 AN: 41448

American (AMR) AF: 0.491 AC: 7498 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2196 AN: 3472

East Asian (EAS) AF: 0.175 AC: 900 AN: 5136

South Asian (SAS) AF: 0.447 AC: 2152 AN: 4816

European-Finnish (FIN) AF: 0.540 AC: 5708 AN: 10566

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38834 AN: 67928

Other (OTH) AF: 0.521 AC: 1101 AN: 2114

Alfa AF: 0.557 Hom.: 103844

Bravo AF: 0.528

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-2.2
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: rs762178; hg19: chr21-34399401; COSMIC: COSV60972530; COSMIC: COSV60972530;