4-140543515-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_153702.4(ELMOD2):c.665A>G(p.Glu222Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,606,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000027 ( 0 hom. )
Consequence
ELMOD2
NM_153702.4 missense
NM_153702.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 5.97
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.033274233).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELMOD2 | NM_153702.4 | c.665A>G | p.Glu222Gly | missense_variant | 8/9 | ENST00000323570.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELMOD2 | ENST00000323570.8 | c.665A>G | p.Glu222Gly | missense_variant | 8/9 | 1 | NM_153702.4 | P1 | |
ELMOD2 | ENST00000502290.1 | n.281A>G | non_coding_transcript_exon_variant | 2/3 | 3 | ||||
ELMOD2 | ENST00000512057.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1454668Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 723726
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2022 | The c.665A>G (p.E222G) alteration is located in exon 8 (coding exon 7) of the ELMOD2 gene. This alteration results from a A to G substitution at nucleotide position 665, causing the glutamic acid (E) at amino acid position 222 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of ubiquitination at K225 (P = 0.0356);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at