rs144778786

Positions:

chr17-31318487-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014210.4(EVI2A):c.527A>G(p.Gln176Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,614,056 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 20 hom. )

Consequence

EVI2A
NM_014210.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010436207).

BP6

Variant 17-31318487-T-C is Benign according to our data. Variant chr17-31318487-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 377247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVI2A	NM_014210.4 linkuse as main transcript	c.527A>G	p.Gln176Arg	missense_variant	2/2	ENST00000462804.3
NF1	NM_001042492.3 linkuse as main transcript	c.4836-7333T>C		intron_variant		ENST00000358273.9
EVI2A	NM_001003927.3 linkuse as main transcript	c.596A>G	p.Gln199Arg	missense_variant	3/3
NF1	NM_000267.3 linkuse as main transcript	c.4773-7333T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVI2A	ENST00000462804.3 linkuse as main transcript	c.527A>G	p.Gln176Arg	missense_variant	2/2	1	NM_014210.4	P2	P22794-1
NF1	ENST00000358273.9 linkuse as main transcript	c.4836-7333T>C		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00442

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00246

AC:

618

AN:

250880

Hom.:

AF XY:

0.00244

AC XY:

331

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000436

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00444

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00501

AC:

7324

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

3538

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.000538

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00136

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00615

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00247

AC:

376

AN:

152346

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00442

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00415

Hom.:

Bravo

AF:

0.00257

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00235

AC:

285

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	EVI2A: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 14, 2016	- -

See cases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Apr 01, 2019

This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -

EVI2A-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

.;T;.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.63

T;.;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.0

.;N;N;.

REVEL

Benign

0.12

Sift

Benign

0.73

.;T;T;.

Sift4G

Benign

0.70

T;T;T;T

Polyphen

0.73, 0.86

.;P;P;P

Vest4

0.26

MVP

0.13

MPC

0.20

ClinPred

0.017

GERP RS

4.6

Varity_R

0.12

gMVP

0.039

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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