19-45616553-C-G

Variant names:

• chr19-45616553-C-G
• NM_012155.4:c.1417G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012155.4(EML2):​c.1417G>C​(p.Ala473Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EML2 NM_012155.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37654626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML2	NM_012155.4	c.1417G>C	p.Ala473Pro	missense_variant	Exon 15 of 19	ENST00000245925.8	NP_036287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925.8	c.1417G>C	p.Ala473Pro	missense_variant	Exon 15 of 19	1	NM_012155.4	ENSP00000245925.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2020G>C (p.A674P) alteration is located in exon 18 (coding exon 18) of the EML2 gene. This alteration results from a G to C substitution at nucleotide position 2020, causing the alanine (A) at amino acid position 674 to be replaced by a proline (P). 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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T;.;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.3	.;L;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	.;N;N;.;.
REVEL	Benign	0.16
Sift	Benign	0.22	.;T;T;.;.
Sift4G	Benign	0.27	T;T;T;T;T
Polyphen		0.76	.;P;.;.;.
Vest4		0.67
MutPred		0.30		Loss of catalytic residue at A473 (P = 0.0281);Loss of catalytic residue at A473 (P = 0.0281);.;.;.;
MVP		0.77
MPC		0.53
ClinPred		0.74	D
GERP RS		4.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.34
gMVP		0.58

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: chr19-46119811;