10-68416702-AG-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The ENST00000440722.2(DNA2):c.1084del(p.Phe364SerfsTer8) 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 (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
DNA2
ENST00000440722.2 frameshift
ENST00000440722.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.41
Genes affected
DNA2 (HGNC:2939): (DNA replication helicase/nuclease 2) This gene encodes a member of the DNA2/NAM7 helicase family. The encoded protein is a conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. Mutations in this gene are associated with autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) and Seckel syndrome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0372 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-68416702-AG-A is Pathogenic according to our data. Variant chr10-68416702-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 143932.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-68416702-AG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNA2 | NM_001080449.3 | c.3114+6del | splice_donor_region_variant, intron_variant | ENST00000358410.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNA2 | ENST00000358410.8 | c.3114+6del | splice_donor_region_variant, intron_variant | 1 | NM_001080449.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Ateleiotic dwarfism Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | - | - - |
Seckel syndrome 8 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2014 | - - |
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