Variant 17-31318455-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014210.4(EVI2A):c.559G>A(p.Gly187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,613,970 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 15 hom. )

Consequence

EVI2A
NM_014210.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.54

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011291891).

BP6

Variant 17-31318455-C-T is Benign according to our data. Variant chr17-31318455-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2578786.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVI2A	NM_014210.4 linkuse as main transcript	c.559G>A	p.Gly187Ser	missense_variant	2/2	ENST00000462804.3
NF1	NM_001042492.3 linkuse as main transcript	c.4836-7365C>T		intron_variant		ENST00000358273.9
EVI2A	NM_001003927.3 linkuse as main transcript	c.628G>A	p.Gly210Ser	missense_variant	3/3
NF1	NM_000267.3 linkuse as main transcript	c.4773-7365C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVI2A	ENST00000462804.3 linkuse as main transcript	c.559G>A	p.Gly187Ser	missense_variant	2/2	1	NM_014210.4	P2	P22794-1
NF1	ENST00000358273.9 linkuse as main transcript	c.4836-7365C>T		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

404

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00463

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00289

AC:

726

AN:

250786

Hom.:

AF XY:

0.00308

AC XY:

418

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00337

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00468

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00440

AC:

6427

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

3156

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00378

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00516

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.00265

AC:

404

AN:

152304

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00463

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00269

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00317

AC:

385

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00451

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

EVI2A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.54

T;.;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.92, 0.94

.;P;P;P

Vest4

0.25

MVP

0.15

MPC

0.18

ClinPred

0.022

GERP RS

5.7

Varity_R

0.076

gMVP

0.11

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