21-33027634-C-G

Variant names:

• chr21-33027634-C-G
• rs1233235355
• NM_005806.4:c.772C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005806.4(OLIG2):​c.772C>G​(p.His258Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,315,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H258Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: OLIG2 NM_005806.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.772C>G	p.His258Asp	missense	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.772C>G	p.His258Asp	missense	Exon 2 of 2	ENSP00000371794.3	Q13516
	OLIG2	ENST00000333337.3	TSL:6	c.772C>G	p.His258Asp	missense	Exon 1 of 1	ENSP00000331040.3	Q13516
	OLIG2	ENST00000877220.1		c.772C>G	p.His258Asp	missense	Exon 2 of 2	ENSP00000547279.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000456 AC: 6 AN: 1315838 Hom.: 0 Cov.: 34 AF XY: 0.00000154 AC XY: 1 AN XY: 648696

African (AFR) AF: 0.00 AC: 0 AN: 26416

American (AMR) AF: 0.00 AC: 0 AN: 25168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22952

East Asian (EAS) AF: 0.00 AC: 0 AN: 28240

South Asian (SAS) AF: 0.00 AC: 0 AN: 72182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000573 AC: 6 AN: 1047822

Other (OTH) AF: 0.00 AC: 0 AN: 54480

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.76	D
Eigen	Benign	-0.059
Eigen_PC	Benign	0.000057
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.7
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.28	T
Polyphen		0.28	B
Vest4		0.67
MutPred		0.21		Loss of methylation at R255 (P = 0.0582)
MVP		0.71
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.54
gMVP		0.58
Mutation Taster		=58/42	polymorphism

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: rs1233235355; hg19: chr21-34399942;