rs1555564126
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004247.4(EFTUD2):c.2551del(p.Ala851ProfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
EFTUD2
NM_004247.4 frameshift
NM_004247.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.87
Genes affected
EFTUD2 (HGNC:30858): (elongation factor Tu GTP binding domain containing 2) This gene encodes a GTPase which is a component of the spliceosome complex which processes precursor mRNAs to produce mature mRNAs. Mutations in this gene are associated with mandibulofacial dysostosis with microcephaly. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-44853305-GC-G is Pathogenic according to our data. Variant chr17-44853305-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 488388.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFTUD2 | NM_004247.4 | c.2551del | p.Ala851ProfsTer7 | frameshift_variant | 25/28 | ENST00000426333.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFTUD2 | ENST00000426333.7 | c.2551del | p.Ala851ProfsTer7 | frameshift_variant | 25/28 | 1 | NM_004247.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mandibulofacial dysostosis-microcephaly syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Mar 31, 2017 | A heterozygous deletion variant was identified, NM_004247.3(EFTUD2):c.2551delG in exon 25 of the EFTUD2 gene (chr17:42930673). This deletion is predicted to cause a frameshift from amino acid position 851, introducing a stop codon 7 residues downstream, NP_004238.3(EFTUD2):p.(Ala851ProfsTer7), resulting in loss of normal protein function either through truncation (loss of ~1/10th of the protien) or nonsense-mediated decay. This variant has not been previously observed in our cohort, it is not present in population databases (ExAC/GnomAD) and has not been previously observed in other clinical cases. However, other heterozygous truncating variants downstream of c.2551delG in EFTUD2 gene have been reported as pathogenic in individuals with Mandibulofacial dysostosis (ClinVar). Based on current information, this variant has been classified as LIKELY PATHOGENIC. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at