Variant 21-33027803-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005806.4(OLIG2):c.941G>C(p.Ser314Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OLIG2
NM_005806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.377

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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=0.19157806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG2	NM_005806.4 linkuse as main transcript	c.941G>C	p.Ser314Thr	missense_variant	2/2	ENST00000382357.4	NP_005797.1
OLIG2	XM_005260908.2 linkuse as main transcript	c.941G>C	p.Ser314Thr	missense_variant	2/2		XP_005260965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OLIG2	ENST00000382357.4 linkuse as main transcript	c.941G>C	p.Ser314Thr	missense_variant	2/2	1	NM_005806.4	ENSP00000371794	P1
	ENST00000454622.2 linkuse as main transcript	n.201+43101C>G		intron_variant, non_coding_transcript_variant		2
OLIG2	ENST00000333337.3 linkuse as main transcript	c.941G>C	p.Ser314Thr	missense_variant	1/1			ENSP00000331040	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1274282

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

624436

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.941G>C (p.S314T) alteration is located in exon 2 (coding exon 1) of the OLIG2 gene. This alteration results from a G to C substitution at nucleotide position 941, causing the serine (S) at amino acid position 314 to be replaced by a threonine (T). 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

0.083

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.32

.;T

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.11

Sift

Benign

0.48

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.0050

B;B

Vest4

0.078

MutPred

0.068

Loss of glycosylation at S314 (P = 0.0286);Loss of glycosylation at S314 (P = 0.0286);

MVP

0.48

ClinPred

0.14

GERP RS

0.68

Varity_R

0.053

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over