Genetic Variant EVI2A:c.-1C>G (chr17-31319014-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001003927.3(EVI2A):c.69C>G(p.Ser23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,591,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

EVI2A
NM_001003927.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

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:

ENSG00000265118 (HGNC:):

ENSG00000265118 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025758117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI2A	NM_014210.4 link	c.-1C>G		5_prime_UTR_variant	Exon 2 of 2	ENST00000462804.3	NP_055025.2	P22794-1
NF1	NM_001042492.3 link	c.4836-6806G>C		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
EVI2A	NM_001003927.3 link	c.69C>G	p.Ser23Arg	missense_variant	Exon 3 of 3		NP_001003927.1	P22794-2
NF1	NM_000267.3 link	c.4773-6806G>C		intron_variant	Intron 35 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVI2A	ENST00000462804.3 link	c.-1C>G	5_prime_UTR_variant	Exon 2 of 2	1	NM_014210.4	ENSP00000420557.3	P22794-1
NF1	ENST00000358273.9 link	c.4836-6806G>C	intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4	P21359-1
ENSG00000265118	ENST00000578584.5 link	c.-229C>G	upstream_gene_variant		2		ENSP00000463981.2	J3QR06

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

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:

0.000478

GnomAD3 exomes

AF:

0.0000605

AC:

AN:

231562

Hom.:

AF XY:

0.0000477

AC XY:

AN XY:

125804

show subpopulations

Gnomad AFR exome

AF:

0.000437

Gnomad AMR exome

AF:

0.000228

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:

0.0000146

AC:

AN:

1439174

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

715178

show subpopulations

Gnomad4 AFR exome

AF:

0.000277

Gnomad4 AMR exome

AF:

0.000270

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:

0.0000168

GnomAD4 genome

AF:

0.000217

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.000981

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:

0.000473

ExAC

AF:

0.0000659

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.7

DANN

Benign

0.80

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.24

M_CAP

Benign

0.0042

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.99

PROVEAN

Benign

0.020

REVEL

Benign

0.014

Sift

Benign

0.068

Polyphen

0.044

Vest4

0.19

MutPred

0.26

Gain of catalytic residue at S23 (P = 0.012);

MVP

0.17

MPC

0.032

ClinPred

0.030

GERP RS

1.4

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over