17-31304902-T-A

Variant summary

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

The NM_006495.4(EVI2B):c.708A>T(p.Gln236His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

EVI2B
NM_006495.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220

Variant links:

Genes affected

EVI2B (HGNC:3500): (ecotropic viral integration site 2B) Involved in positive regulation of granulocyte differentiation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI2B links:

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 links:

Genome browser will be placed here

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=0.18863958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVI2B	NM_006495.4 linkuse as main transcript	c.708A>T	p.Gln236His	missense_variant	2/2	ENST00000330927.5
NF1	NM_001042492.3 linkuse as main transcript	c.4836-20918T>A		intron_variant		ENST00000358273.9
NF1	NM_000267.3 linkuse as main transcript	c.4773-20918T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVI2B	ENST00000330927.5 linkuse as main transcript	c.708A>T	p.Gln236His	missense_variant	2/2	1	NM_006495.4	P1	P34910-1
NF1	ENST00000358273.9 linkuse as main transcript	c.4836-20918T>A		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250892

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

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:

0.0000497

GnomAD4 genome

AF:

0.000177

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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 27, 2022

The c.708A>T (p.Q236H) alteration is located in exon 2 (coding exon 1) of the EVI2B gene. This alteration results from a A to T substitution at nucleotide position 708, causing the glutamine (Q) at amino acid position 236 to be replaced by a histidine (H). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

0.010

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.62

M_CAP

Benign

0.021

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.15

Sift

Uncertain

0.0070

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.98

D;D

Vest4

0.16

MVP

0.74

MPC

0.039

ClinPred

0.41

GERP RS

0.67

Varity_R

0.21

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over