rs536749831
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
The NM_004247.4(EFTUD2):c.1058+3_1058+7del variant causes a splice donor 5th base, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,613,102 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0052 ( 4 hom., cov: 31)
Exomes 𝑓: 0.0065 ( 33 hom. )
Consequence
EFTUD2
NM_004247.4 splice_donor_5th_base, intron
NM_004247.4 splice_donor_5th_base, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.75
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 Benign. Variant got -15 ACMG points.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP6
?
Variant 17-44868279-CTACTT-C is Benign according to our data. Variant chr17-44868279-CTACTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 259250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-44868279-CTACTT-C is described in Lovd as [Likely_pathogenic]. Variant chr17-44868279-CTACTT-C is described in Lovd as [Benign]. Variant chr17-44868279-CTACTT-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00518 (789/152234) while in subpopulation NFE AF= 0.00717 (488/68020). AF 95% confidence interval is 0.00665. There are 4 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 789 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFTUD2 | NM_004247.4 | c.1058+3_1058+7del | splice_donor_5th_base_variant, intron_variant | ENST00000426333.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFTUD2 | ENST00000426333.7 | c.1058+3_1058+7del | splice_donor_5th_base_variant, intron_variant | 1 | NM_004247.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00519 AC: 789AN: 152118Hom.: 4 Cov.: 31
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GnomAD3 exomes AF: 0.00542 AC: 1359AN: 250748Hom.: 4 AF XY: 0.00526 AC XY: 713AN XY: 135536
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GnomAD4 exome AF: 0.00655 AC: 9562AN: 1460868Hom.: 33 AF XY: 0.00634 AC XY: 4610AN XY: 726734
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GnomAD4 genome ? AF: 0.00518 AC: 789AN: 152234Hom.: 4 Cov.: 31 AF XY: 0.00512 AC XY: 381AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:6
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2019 | This variant is associated with the following publications: (PMID: 23188108, 27895973) - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 31, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | EFTUD2: BP4, BS1, BS2 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Mandibulofacial dysostosis-microcephaly syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 11, 2021 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at