21-33029069-T-G

Variant names:

• chr21-33029069-T-G
• rs13046814
• NM_005806.4:c.*1235T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005806.4(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 NM_005806.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 5 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 -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.

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.*1235T>G		3_prime_UTR	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.*1235T>G		3_prime_UTR	Exon 2 of 2	ENSP00000371794.3	Q13516
	OLIG2	ENST00000333337.3	TSL:6	c.*1235T>G		3_prime_UTR	Exon 1 of 1	ENSP00000331040.3	Q13516
	OLIG2	ENST00000877220.1		c.*1235T>G		3_prime_UTR	Exon 2 of 2	ENSP00000547279.1

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

African (AFR) AF: 0.105 AC: 345 AN: 3280

American (AMR) AF: 0.217 AC: 453 AN: 2088

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1705 AN: 4442

East Asian (EAS) AF: 0.0750 AC: 754 AN: 10050

South Asian (SAS) AF: 0.290 AC: 183 AN: 630

European-Finnish (FIN) AF: 0.293 AC: 4309 AN: 14726

Middle Eastern (MID) AF: 0.346 AC: 150 AN: 434

European-Non Finnish (NFE) AF: 0.368 AC: 15866 AN: 43172

Other (OTH) AF: 0.316 AC: 1869 AN: 5922

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

African (AFR) AF: 0.103 AC: 4270 AN: 41544

American (AMR) AF: 0.234 AC: 3583 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3470

East Asian (EAS) AF: 0.0589 AC: 306 AN: 5192

South Asian (SAS) AF: 0.305 AC: 1476 AN: 4832

European-Finnish (FIN) AF: 0.308 AC: 3258 AN: 10584

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24727 AN: 68024

Other (OTH) AF: 0.295 AC: 624 AN: 2116

Alfa AF: 0.269 Hom.: 3201

Bravo AF: 0.248

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.092
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: rs13046814; hg19: chr21-34401377;