chr7-107891268-T-TG
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000108.5(DLD):c.19dup(p.Val7GlyfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R6R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Consequence
DLD
NM_000108.5 frameshift
NM_000108.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.29
Genes affected
DLD (HGNC:2898): (dihydrolipoamide dehydrogenase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 66 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-107891268-T-TG is Pathogenic according to our data. Variant chr7-107891268-T-TG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1726142.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLD | NM_000108.5 | c.19dup | p.Val7GlyfsTer35 | frameshift_variant | 1/14 | ENST00000205402.10 | |
DLD | NM_001289751.1 | c.19dup | p.Val7GlyfsTer35 | frameshift_variant | 1/13 | ||
DLD | NM_001289752.1 | c.19dup | p.Val7GlyfsTer35 | frameshift_variant | 1/13 | ||
DLD | NM_001289750.1 | c.-130dup | 5_prime_UTR_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLD | ENST00000205402.10 | c.19dup | p.Val7GlyfsTer35 | frameshift_variant | 1/14 | 1 | NM_000108.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pyruvate dehydrogenase E3 deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | May 18, 2022 | NM_000108.3(DLD):c.19dupG(V7Gfs*35) is expected to be pathogenic in the context of dihydrolipoamide dehydrogenase deficiency. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in DLD, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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
Publications
No publications associated with this variant yet.