Variant rs1545040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012155.4(EML2):c.705G>T(p.Glu235Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,613,664 control chromosomes in the GnomAD database, including 3,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.084 ( 1045 hom., cov: 30)

Exomes 𝑓: 0.039 ( 2919 hom. )

Consequence

EML2
NM_012155.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.76

Variant links:

Genes affected

EML2 (HGNC:18035): (EMAP like 2) Enables microtubule binding activity. Involved in negative regulation of microtubule polymerization and regulation of microtubule nucleation. Colocalizes with mitotic spindle. [provided by Alliance of Genome Resources, Apr 2022]

EML2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020727217).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML2	NM_012155.4 linkuse as main transcript	c.705G>T	p.Glu235Asp	missense_variant	8/19	ENST00000245925.8	NP_036287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8 linkuse as main transcript	c.705G>T	p.Glu235Asp	missense_variant	8/19	1	NM_012155.4	ENSP00000245925	A1	O95834-1

Frequencies

GnomAD3 genomes

AF:

0.0839

AC:

12744

AN:

151902

Hom.:

1046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0703

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.00576

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0780

GnomAD3 exomes

AF:

0.0620

AC:

15584

AN:

251224

Hom.:

1042

AF XY:

0.0621

AC XY:

8437

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.0467

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.00638

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0386

AC:

56359

AN:

1461644

Hom.:

2919

Cov.:

AF XY:

0.0408

AC XY:

29630

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.0518

Gnomad4 ASJ exome

AF:

0.0529

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.00807

Gnomad4 NFE exome

AF:

0.0205

Gnomad4 OTH exome

AF:

0.0506

GnomAD4 genome

AF:

0.0839

AC:

12753

AN:

152020

Hom.:

1045

Cov.:

AF XY:

0.0853

AC XY:

6343

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.0702

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.00576

Gnomad4 NFE

AF:

0.0214

Gnomad4 OTH

AF:

0.0772

Alfa

AF:

0.0364

Hom.:

577

Bravo

AF:

0.0935

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.202

AC:

889

ESP6500EA

AF:

0.0237

AC:

204

ExAC

AF:

0.0657

AC:

7975

Asia WGS

AF:

0.119

AC:

414

AN:

3478

EpiCase

AF:

0.0234

EpiControl

AF:

0.0255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.27

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0038

T;T;.;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.65

T;T;T;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.71

.;N;.;.;.;.

MutationTaster

Benign

0.032

P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

.;N;N;.;.;.

REVEL

Benign

0.15

Sift

Benign

0.62

.;T;T;.;.;.

Sift4G

Benign

0.45

T;T;T;T;T;T

Polyphen

0.0020

.;B;.;.;.;.

Vest4

0.073

MutPred

0.091

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;.;.;.;

MPC

0.23

ClinPred

0.0028

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.27

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