Genetic Variant NM_005806.4:c.-63+382C>T (chr21-33026408-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005806.4(OLIG2):c.-63+382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 174,490 control chromosomes in the GnomAD database, including 45,710 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 0.72 ( 40707 hom., cov: 30)

Exomes 𝑓: 0.65 ( 5003 hom. )

Consequence

OLIG2
NM_005806.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

Publications

5 publications found

Variant links:

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]

OLIG2 links:

ENSG00000227757 (HGNC:):

ENSG00000227757 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 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.-63+382C>T		intron	N/A	NP_005797.1	Q13516

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OLIG2	ENST00000382357.4	TSL:1 MANE Select	c.-63+382C>T	intron	N/A	ENSP00000371794.3	Q13516
OLIG2	ENST00000333337.3	TSL:6	c.-455C>T	5_prime_UTR	Exon 1 of 1	ENSP00000331040.3	Q13516
OLIG2	ENST00000877220.1		c.-62-393C>T	intron	N/A	ENSP00000547279.1

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110031

AN:

151880

Hom.:

40667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.855

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.677

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.728

GnomAD4 exome

AF:

0.650

AC:

14620

AN:

22492

Hom.:

5003

Cov.:

AF XY:

0.651

AC XY:

7743

AN XY:

11894

show subpopulations

African (AFR)

AF:

0.789

AC:

180

AN:

228

American (AMR)

AF:

0.626

AC:

1782

AN:

2846

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

307

AN:

406

East Asian (EAS)

AF:

0.302

AC:

240

AN:

794

South Asian (SAS)

AF:

0.699

AC:

2752

AN:

3938

European-Finnish (FIN)

AF:

0.593

AC:

408

AN:

688

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.659

AC:

8235

AN:

12500

Other (OTH)

AF:

0.651

AC:

674

AN:

1036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

242

485

727

970

1212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.725

AC:

110127

AN:

151998

Hom.:

40707

Cov.:

AF XY:

0.722

AC XY:

53669

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.856

AC:

35482

AN:

41470

American (AMR)

AF:

0.676

AC:

10331

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

2711

AN:

3470

East Asian (EAS)

AF:

0.383

AC:

1973

AN:

5148

South Asian (SAS)

AF:

0.721

AC:

3472

AN:

4816

European-Finnish (FIN)

AF:

0.651

AC:

6886

AN:

10570

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47116

AN:

67938

Other (OTH)

AF:

0.725

AC:

1528

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1493

2987

4480

5974

7467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.710

Hom.:

6382

Bravo

AF:

0.729

Asia WGS

AF:

0.579

AC:

2013

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.0

(source)

DANN

Benign

0.69

PhyloP100

0.24

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over