Genetic Variant EML2:c.1824+12G>A (chr19-45613529-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012155.4(EML2):c.1824+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,613,418 control chromosomes in the GnomAD database, including 1,842 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 553 hom., cov: 32)

Exomes 𝑓: 0.028 ( 1289 hom. )

Consequence

EML2
NM_012155.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.56

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML2	NM_012155.4 link	c.1824+12G>A		intron_variant	Intron 18 of 18	ENST00000245925.8	NP_036287.1	O95834-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8 link	c.1824+12G>A		intron_variant	Intron 18 of 18	1	NM_012155.4	ENSP00000245925.3		O95834-1

Frequencies

GnomAD3 genomes

AF:

0.0583

AC:

8871

AN:

152056

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.0376

Gnomad SAS

AF:

0.0964

Gnomad FIN

AF:

0.00716

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.0498

GnomAD2 exomes

AF:

0.0385

AC:

9646

AN:

250856

AF XY:

0.0398

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0366

Gnomad EAS exome

AF:

0.0339

Gnomad FIN exome

AF:

0.00710

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0373

GnomAD4 exome

AF:

0.0278

AC:

40672

AN:

1461244

Hom.:

1289

Cov.:

AF XY:

0.0298

AC XY:

21628

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.161

AC:

5395

AN:

33474

American (AMR)

AF:

0.0182

AC:

813

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0344

AC:

898

AN:

26096

East Asian (EAS)

AF:

0.0333

AC:

1322

AN:

39680

South Asian (SAS)

AF:

0.0977

AC:

8415

AN:

86164

European-Finnish (FIN)

AF:

0.00838

AC:

447

AN:

53322

Middle Eastern (MID)

AF:

0.0422

AC:

243

AN:

5762

European-Non Finnish (NFE)

AF:

0.0189

AC:

21017

AN:

1111696

Other (OTH)

AF:

0.0352

AC:

2122

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1959

3917

5876

7834

9793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

956

1912

2868

3824

4780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0584

AC:

8880

AN:

152174

Hom.:

553

Cov.:

AF XY:

0.0584

AC XY:

4349

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.148

AC:

6138

AN:

41464

American (AMR)

AF:

0.0286

AC:

437

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3468

East Asian (EAS)

AF:

0.0379

AC:

196

AN:

5178

South Asian (SAS)

AF:

0.0969

AC:

468

AN:

4832

European-Finnish (FIN)

AF:

0.00716

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0195

AC:

1324

AN:

68016

Other (OTH)

AF:

0.0493

AC:

104

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

382

765

1147

1530

1912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0318

Hom.:

233

Bravo

AF:

0.0635

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.010

(source)

DANN

Benign

0.58

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over