chr21-33027694-G-A

Position:

• chr21-33027694-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005806.4(OLIG2):​c.832G>A​(p.Gly278Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000823 in 1,215,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: OLIG2 NM_005806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.717

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25471085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLIG2	NM_005806.4	c.832G>A	p.Gly278Ser	missense_variant	2/2	ENST00000382357.4
OLIG2	XM_005260908.2	c.832G>A	p.Gly278Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLIG2	ENST00000382357.4	c.832G>A	p.Gly278Ser	missense_variant	2/2	1	NM_005806.4	P1
	ENST00000454622.2	n.201+43210C>T		intron_variant, non_coding_transcript_variant		2
OLIG2	ENST00000333337.3	c.832G>A	p.Gly278Ser	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1215086 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 592028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000201

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.832G>A (p.G278S) alteration is located in exon 2 (coding exon 1) of the OLIG2 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the glycine (G) at amino acid position 278 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.50	.;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	0.65	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.13
Sift	Benign	0.12	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.89	P;P
Vest4		0.29
MutPred		0.16		Gain of glycosylation at G278 (P = 0.0089);Gain of glycosylation at G278 (P = 0.0089);
MVP		0.58
ClinPred		0.29	T
GERP RS		2.2
Varity_R		0.075
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-34400002;