21-33029069-T-G

Position:

• chr21-33029069-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000382357.4(OLIG2):​c.*1235T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 237,012 control chromosomes in the GnomAD database, including 10,557 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 0.26 (6201 hom., cov: 34)
  • Exomes 𝑓: 0.30 (4356 hom.)
• Consequence: OLIG2 ENST00000382357.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG2	NM_005806.4	c.*1235T>G		3_prime_UTR_variant	2/2	ENST00000382357.4	NP_005797.1
OLIG2	XM_005260908.2	c.*1235T>G		3_prime_UTR_variant	2/2		XP_005260965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLIG2	ENST00000382357.4	c.*1235T>G		3_prime_UTR_variant	2/2	1	NM_005806.4	ENSP00000371794	P1
	ENST00000454622.2	n.201+41835A>C		intron_variant, non_coding_transcript_variant		2
OLIG2	ENST00000333337.3	c.*1235T>G		3_prime_UTR_variant	1/1			ENSP00000331040	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39742 AN: 152150 Hom.: 6203 Cov.: 34

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.302 AC: 25634 AN: 84744 Hom.: 4356 Cov.: 0 AF XY: 0.306 AC XY: 12010 AN XY: 39276

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.0750

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.261 AC: 39745 AN: 152268 Hom.: 6201 Cov.: 34 AF XY: 0.259 AC XY: 19284 AN XY: 74440

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.0589

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.295

Alfa AF: 0.257 Hom.: 1964

Bravo AF: 0.248

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.75

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: rs13046814; hg19: chr21-34401377;