Variant 17-31318338-C-T 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_014210.4(EVI2A):c.676G>A(p.Gly226Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,444 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EVI2A
NM_014210.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.748

Variant links:

Genes affected

EVI2A (HGNC:3499): (ecotropic viral integration site 2A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI2A 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:

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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=0.09881973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVI2A	NM_014210.4 linkuse as main transcript	c.676G>A	p.Gly226Arg	missense_variant	2/2	ENST00000462804.3
NF1	NM_001042492.3 linkuse as main transcript	c.4836-7482C>T		intron_variant		ENST00000358273.9
EVI2A	NM_001003927.3 linkuse as main transcript	c.745G>A	p.Gly249Arg	missense_variant	3/3
NF1	NM_000267.3 linkuse as main transcript	c.4773-7482C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVI2A	ENST00000462804.3 linkuse as main transcript	c.676G>A	p.Gly226Arg	missense_variant	2/2	1	NM_014210.4	P2	P22794-1
NF1	ENST00000358273.9 linkuse as main transcript	c.4836-7482C>T		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724940

show subpopulations

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:

9.00e-7

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

Sep 22, 2023

The c.745G>A (p.G249R) alteration is located in exon 3 (coding exon 2) of the EVI2A gene. This alteration results from a G to A substitution at nucleotide position 745, causing the glycine (G) at amino acid position 249 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.97

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.71

T;.;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

D;D;N;N;N;N

PrimateAI

Benign

0.30

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.053, 0.043

.;B;B;B

Vest4

0.12

MutPred

0.53

.;Gain of helix (P = 0.0078);.;Gain of helix (P = 0.0078);

MVP

0.44

MPC

0.039

ClinPred

0.24

GERP RS

4.4

Varity_R

0.19

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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