Genetic Variant ELMOD2:p.Val115Glu (chr4-140537486-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153702.4(ELMOD2):c.344T>A(p.Val115Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000818 in 1,589,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

ELMOD2
NM_153702.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

Variant links:

Genes affected

ELMOD2 (HGNC:28111): (ELMO domain containing 2) This gene encodes one of six engulfment and motility (ELMO) domain-containing proteins. This gene is thought to play a role in antiviral responses. Mutations in this gene may be involved in the cause of familial idiopathic pulmonary fibrosis. [provided by RefSeq, Sep 2010]

ELMOD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.38820308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD2	NM_153702.4 link	c.344T>A	p.Val115Glu	missense_variant	Exon 5 of 9	ENST00000323570.8	NP_714913.1	Q8IZ81

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELMOD2	ENST00000323570.8 link	c.344T>A	p.Val115Glu	missense_variant	Exon 5 of 9	1	NM_153702.4	ENSP00000326342.3	Q8IZ81
ELMOD2	ENST00000502397.5 link	c.344T>A	p.Val115Glu	missense_variant	Exon 5 of 6	5		ENSP00000422582.1	D6RBS5
ELMOD2	ENST00000513606.1 link	c.113T>A	p.Val38Glu	missense_variant	Exon 4 of 5	4		ENSP00000427592.1	D6RHX2
ELMOD2	ENST00000512057.1 link	n.489T>A		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000835

AC:

AN:

1437316

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714224

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.0000841

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 04, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.344T>A (p.V115E) alteration is located in exon 5 (coding exon 4) of the ELMOD2 gene. This alteration results from a T to A substitution at nucleotide position 344, causing the valine (V) at amino acid position 115 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.16

T;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.0010

B;.;.

Vest4

0.37

MVP

0.38

MPC

0.060

ClinPred

0.94

GERP RS

4.6

Varity_R

0.51

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over