Genetic Variant NM_012155.4: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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012155.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EML2	NM_012155.4	MANE Select	c.1824+12G>A	intron	N/A	NP_036287.1	O95834-1
EML2	NM_001193268.3		c.2427+12G>A	intron	N/A	NP_001180197.1	O95834-3
EML2	NM_001352052.1		c.2424+12G>A	intron	N/A	NP_001338981.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EML2	ENST00000245925.8	TSL:1 MANE Select	c.1824+12G>A	intron	N/A	ENSP00000245925.3	O95834-1
EML2	ENST00000589876.5	TSL:1	c.1824+12G>A	intron	N/A	ENSP00000464789.1	K7EIK7
EML2	ENST00000587152.6	TSL:2	c.2427+12G>A	intron	N/A	ENSP00000468312.1	O95834-3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over