rs1545040

Variant names:

• chr19-45626741-C-A
• rs1545040
• NM_012155.4:c.705G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-45626741-C-A
• chr19-45626741-C-G
• chr19-45626741-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (1045 hom., cov: 30)
  • Exomes 𝑓: 0.039 (2919 hom.)
• Consequence: EML2 NM_012155.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EML2	NM_012155.4	c.705G>T	p.Glu235Asp	missense_variant	Exon 8 of 19	ENST00000245925.8	NP_036287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8	c.705G>T	p.Glu235Asp	missense_variant	Exon 8 of 19	1	NM_012155.4	ENSP00000245925.3

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12744 AN: 151902 Hom.: 1046 Cov.: 30

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

GnomAD2 exomes AF: 0.0620 AC: 15584 AN: 251224 AF XY: 0.0621

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 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.: 31 AF XY: 0.0408 AC XY: 29630 AN XY: 727106

African (AFR) AF: 0.212 AC: 7109 AN: 33464

American (AMR) AF: 0.0518 AC: 2315 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 1383 AN: 26126

East Asian (EAS) AF: 0.197 AC: 7836 AN: 39688

South Asian (SAS) AF: 0.128 AC: 11073 AN: 86210

European-Finnish (FIN) AF: 0.00807 AC: 431 AN: 53404

Middle Eastern (MID) AF: 0.0628 AC: 362 AN: 5766

European-Non Finnish (NFE) AF: 0.0205 AC: 22797 AN: 1111904

Other (OTH) AF: 0.0506 AC: 3053 AN: 60374

GnomAD4 genome AF: 0.0839 AC: 12753 AN: 152020 Hom.: 1045 Cov.: 30 AF XY: 0.0853 AC XY: 6343 AN XY: 74322

African (AFR) AF: 0.201 AC: 8315 AN: 41400

American (AMR) AF: 0.0702 AC: 1071 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3472

East Asian (EAS) AF: 0.165 AC: 850 AN: 5146

South Asian (SAS) AF: 0.132 AC: 638 AN: 4822

European-Finnish (FIN) AF: 0.00576 AC: 61 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0214 AC: 1453 AN: 68018

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0409 Hom.: 1422

Bravo AF: 0.0935

TwinsUK AF: 0.0165 AC: 61

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	T
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	N
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	T
MutationAssessor	Benign	0.71	.;N;.;.;.;.
PhyloP100		-2.8
PrimateAI	Benign	0.46	T
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	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.27
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1545040; hg19: chr19-46129999; COSMIC: COSV55597587; COSMIC: COSV55597587;