chr19-45616553-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML2	NM_012155.4	MANE Select	c.1417G>C	p.Ala473Pro	missense	Exon 15 of 19	NP_036287.1	O95834-1
	EML2	NM_001193268.3		c.2020G>C	p.Ala674Pro	missense	Exon 18 of 22	NP_001180197.1	O95834-3
	EML2	NM_001352052.1		c.2017G>C	p.Ala673Pro	missense	Exon 18 of 22	NP_001338981.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML2	ENST00000245925.8	TSL:1 MANE Select	c.1417G>C	p.Ala473Pro	missense	Exon 15 of 19	ENSP00000245925.3	O95834-1
	EML2	ENST00000589876.5	TSL:1	c.1417G>C	p.Ala473Pro	missense	Exon 15 of 19	ENSP00000464789.1	K7EIK7
	EML2	ENST00000587152.6	TSL:2	c.2020G>C	p.Ala674Pro	missense	Exon 18 of 22	ENSP00000468312.1	O95834-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Benign	0.22	T
Sift4G	Benign	0.27	T
Polyphen		0.76	P
Vest4		0.67
MutPred		0.30		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
Mutation Taster		=68/32	polymorphism

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

hg19: chr19-46119811;