rs7252175

Positions:

• chr19-45629998-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000245925.8(EML2):​c.559C>T​(p.Leu187Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,610,508 control chromosomes in the GnomAD database, including 13,241 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1380 hom., cov: 29)
  • Exomes 𝑓: 0.13 (11861 hom.)
• Consequence: EML2 ENST00000245925.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017551184).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML2	NM_012155.4	c.559C>T	p.Leu187Phe	missense_variant	7/19	ENST00000245925.8	NP_036287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8	c.559C>T	p.Leu187Phe	missense_variant	7/19	1	NM_012155.4	ENSP00000245925	A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20153 AN: 151820 Hom.: 1376 Cov.: 29

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.138

GnomAD3 exomes AF: 0.126 AC: 31755 AN: 251176 Hom.: 2154 AF XY: 0.124 AC XY: 16851 AN XY: 135730

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.125 AC: 182781 AN: 1458570 Hom.: 11861 Cov.: 32 AF XY: 0.125 AC XY: 90343 AN XY: 725640

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0980

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.133 AC: 20183 AN: 151938 Hom.: 1380 Cov.: 29 AF XY: 0.129 AC XY: 9586 AN XY: 74294

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.137

Alfa AF: 0.129 Hom.: 3142

Bravo AF: 0.138

TwinsUK AF: 0.131 AC: 486

ALSPAC AF: 0.125 AC: 483

ESP6500AA AF: 0.153 AC: 674

ESP6500EA AF: 0.133 AC: 1141

ExAC AF: 0.126 AC: 15259

Asia WGS AF: 0.118 AC: 409 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;T;.;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.2	.;M;.;.;.
MutationTaster	Benign	0.0000041	P;P;P;P
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.4	.;D;D;.;.
REVEL	Benign	0.24
Sift	Uncertain	0.0020	.;D;D;.;.
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.23
MPC		0.89
ClinPred		0.052	T
GERP RS		4.7
Varity_R		0.55
gMVP		0.70

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

Other links and lift over

dbSNP: rs7252175; hg19: chr19-46133256; COSMIC: COSV55599633; COSMIC: COSV55599633;