Variant 19-45617679-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012155.4(EML2):c.1273G>A(p.Gly425Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000268 in 1,613,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

EML2
NM_012155.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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:

EML2 (HGNC:):

EML2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28065306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML2	NM_012155.4 linkuse as main transcript	c.1273G>A	p.Gly425Ser	missense_variant	13/19	ENST00000245925.8	NP_036287.1	O95834-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8 linkuse as main transcript	c.1273G>A	p.Gly425Ser	missense_variant	13/19	1	NM_012155.4	ENSP00000245925.3		O95834-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

250454

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000274

AC:

400

AN:

1461454

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.000318

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000210

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000237

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

Jan 18, 2023

The c.1876G>A (p.G626S) alteration is located in exon 16 (coding exon 16) of the EML2 gene. This alteration results from a G to A substitution at nucleotide position 1876, causing the glycine (G) at amino acid position 626 to be replaced by a serine (S). 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

0.091

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T;.;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

.;M;.;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.8

.;D;D;.;.

REVEL

Benign

0.18

Sift

Benign

0.082

.;T;T;.;.

Sift4G

Benign

0.25

T;T;T;T;T

Polyphen

1.0

.;D;.;.;.

Vest4

0.54

MVP

0.57

MPC

0.25

ClinPred

0.13

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.55

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