17-44851717-C-CG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_004247.4(EFTUD2):​c.2815dupC​(p.Arg939ProfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EFTUD2
NM_004247.4 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.76
Variant links:
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 Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0356 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-44851717-C-CG is Pathogenic according to our data. Variant chr17-44851717-C-CG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3358960.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EFTUD2NM_004247.4 linkc.2815dupC p.Arg939ProfsTer2 frameshift_variant Exon 27 of 28 ENST00000426333.7 NP_004238.3 Q15029-1B3KX19
EFTUD2NM_001258353.2 linkc.2815dupC p.Arg939ProfsTer2 frameshift_variant Exon 27 of 28 NP_001245282.1 Q15029-1
EFTUD2NM_001258354.2 linkc.2785dupC p.Arg929ProfsTer2 frameshift_variant Exon 27 of 28 NP_001245283.1 Q15029-3
EFTUD2NM_001142605.2 linkc.2710dupC p.Arg904ProfsTer2 frameshift_variant Exon 26 of 27 NP_001136077.1 Q15029-2B3KX19

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EFTUD2ENST00000426333.7 linkc.2815dupC p.Arg939ProfsTer2 frameshift_variant Exon 27 of 28 1 NM_004247.4 ENSP00000392094.1 Q15029-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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
Apr 22, 2024
Institute of Human Genetics, University of Leipzig Medical Center
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Criteria applied: PVS1,PM2_SUP -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr17-42929085; API