rs1005573

Positions:

• chr21-33026408-C-T
• chr21-33026408-C-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG2	NM_005806.4	c.-63+382C>T		intron_variant		ENST00000382357.4	NP_005797.1
OLIG2	XM_005260908.2	c.-63+148C>T		intron_variant			XP_005260965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLIG2	ENST00000382357.4	c.-63+382C>T		intron_variant		1	NM_005806.4	ENSP00000371794.3
OLIG2	ENST00000333337	c.-455C>T		5_prime_UTR_variant	1/1			ENSP00000331040.3
OLIG2	ENST00000430860.1	c.-63+148C>T		intron_variant		4		ENSP00000391183.1
ENSG00000227757	ENST00000454622.2	n.201+44496G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110031 AN: 151880 Hom.: 40667 Cov.: 30

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.: 0 AF XY: 0.651 AC XY: 7743 AN XY: 11894

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.699

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.725 AC: 110127 AN: 151998 Hom.: 40707 Cov.: 30 AF XY: 0.722 AC XY: 53669 AN XY: 74298

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.725

Alfa AF: 0.706 Hom.: 6098

Bravo AF: 0.729

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.69

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: rs1005573; hg19: chr21-34398716;