20-46371382-C-T

Position:

• chr20-46371382-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_133171.5(ELMO2):​c.1771G>A​(p.Glu591Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELMO2 NM_133171.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92

Genes affected

ELMO2 (HGNC:17233): (engulfment and cell motility 2) The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein. Similarity to a C. elegans protein suggests that this protein may function in phagocytosis of apoptotic cells and in cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ELMO2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ELMO2. . Gene score misZ 3.2732 (greater than the threshold 3.09). Trascript score misZ 4.666 (greater than threshold 3.09). GenCC has associacion of gene with Ramon syndrome, primary intraosseous venous malformation.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMO2	NM_133171.5	c.1771G>A	p.Glu591Lys	missense_variant	19/22	ENST00000290246.11	NP_573403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMO2	ENST00000290246.11	c.1771G>A	p.Glu591Lys	missense_variant	19/22	1	NM_133171.5	ENSP00000290246.6
ELMO2	ENST00000372176.5	c.1507G>A	p.Glu503Lys	missense_variant	19/22	5		ENSP00000361249.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.1771G>A (p.E591K) alteration is located in exon 19 (coding exon 17) of the ELMO2 gene. This alteration results from a G to A substitution at nucleotide position 1771, causing the glutamic acid (E) at amino acid position 591 to be replaced by a lysine (K). 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	0.21
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T;.;.;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.50	D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.8	L;.;.;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.55	N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.24	T;T;D;T;T
Sift4G	Benign	0.85	T;T;T;T;T
Polyphen		0.79	P;.;.;P;.
Vest4		0.61
MVP		0.63
MPC		0.88
ClinPred		0.66	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr20-45000021;