chr19-45613547-C-A

Position:

• chr19-45613547-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012155.4(EML2):​c.1818G>T​(p.Gln606His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EML2 NM_012155.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.251

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1789828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML2	NM_012155.4	c.1818G>T	p.Gln606His	missense_variant	18/19	ENST00000245925.8	NP_036287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8	c.1818G>T	p.Gln606His	missense_variant	18/19	1	NM_012155.4	ENSP00000245925	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.2421G>T (p.Q807H) alteration is located in exon 21 (coding exon 21) of the EML2 gene. This alteration results from a G to T substitution at nucleotide position 2421, causing the glutamine (Q) at amino acid position 807 to be replaced by a histidine (H). 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	0.25
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T;T;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T;D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	.;D;D;.
REVEL	Benign	0.052
Sift	Benign	0.10	.;T;T;.
Sift4G	Benign	0.075	T;T;T;T
Polyphen		0.0010	.;B;.;.
Vest4		0.38
MutPred		0.25		Gain of disorder (P = 0.1309);Gain of disorder (P = 0.1309);.;.;
MVP		0.43
MPC		0.25
ClinPred		0.80	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-46116805;