rs762178

Positions:

• chr21-33027093-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG2	NM_005806.4	c.231A>G	p.Ser77Ser	synonymous_variant	2/2	ENST00000382357.4	NP_005797.1
OLIG2	XM_005260908.2	c.231A>G	p.Ser77Ser	synonymous_variant	2/2		XP_005260965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLIG2	ENST00000382357.4	c.231A>G	p.Ser77Ser	synonymous_variant	2/2	1	NM_005806.4	ENSP00000371794.3
OLIG2	ENST00000333337.3	c.231A>G	p.Ser77Ser	synonymous_variant	1/1	6		ENSP00000331040.3
ENSG00000227757	ENST00000454622.2	n.201+43811T>C		intron_variant		2
OLIG2	ENST00000430860.1	c.*44A>G		downstream_gene_variant		4		ENSP00000391183.1

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

GnomAD3 exomes AF: 0.511 AC: 123283 AN: 241414 Hom.: 32889 AF XY: 0.514 AC XY: 67331 AN XY: 131056

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 SAS exome AF: 0.472

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

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.533

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

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.521

Alfa AF: 0.565 Hom.: 47980

Bravo AF: 0.528

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.2
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs762178; hg19: chr21-34399401; COSMIC: COSV60972530; COSMIC: COSV60972530;