20-46371382-C-T

Position:

• chr20-46371382-C-T

Variant summary

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

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]

ENSG00000273828 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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;