rs199957663

Variant names:

• chr19-45609729-C-A
• rs199957663
• NM_012155.4:c.1884G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-45609729-C-A
• chr19-45609729-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012155.4(EML2):​c.1884G>T​(p.Trp628Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: EML2 NM_012155.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.896
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017731488).

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.1884G>T	p.Trp628Cys	missense	Exon 19 of 19	NP_036287.1	O95834-1
	EML2	NM_001193268.3		c.2487G>T	p.Trp829Cys	missense	Exon 22 of 22	NP_001180197.1	O95834-3
	EML2	NM_001352052.1		c.2484G>T	p.Trp828Cys	missense	Exon 22 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.1884G>T	p.Trp628Cys	missense	Exon 19 of 19	ENSP00000245925.3	O95834-1
	EML2	ENST00000589876.5	TSL:1	c.1825-2223G>T		intron	N/A	ENSP00000464789.1	K7EIK7
	EML2	ENST00000587152.6	TSL:2	c.2487G>T	p.Trp829Cys	missense	Exon 22 of 22	ENSP00000468312.1	O95834-3

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152146 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 250876 AF XY: 0.000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 97 AN: 1461374 Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.000269 AC: 12 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 69 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111828

Other (OTH) AF: 0.000149 AC: 9 AN: 60362

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152146 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.000459 AC: 7 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000383 Hom.: 0

Bravo AF: 0.000193

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.90
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.091
Sift	Benign	0.33	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.56		Loss of sheet (P = 0.1501)
MVP		0.25
MPC		0.37
ClinPred		0.94	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.25
gMVP		0.57
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199957663; hg19: chr19-46112987;