rs1037224921
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173660.5(DOK7):āc.1054C>Gā(p.Leu352Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L352L) has been classified as Likely benign.
Frequency
Consequence
NM_173660.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.1054C>G | p.Leu352Val | missense_variant | 7/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.1054C>G | p.Leu352Val | missense_variant | 7/7 | 1 | NM_173660.5 | P1 | |
DOK7 | ENST00000643608.1 | c.622C>G | p.Leu208Val | missense_variant | 5/8 | ||||
DOK7 | ENST00000515886.5 | c.124C>G | p.Leu42Val | missense_variant | 4/4 | 2 | |||
DOK7 | ENST00000507039.5 | c.*275C>G | 3_prime_UTR_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1420670Hom.: 0 Cov.: 111 AF XY: 0.00 AC XY: 0AN XY: 704386
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 352 of the DOK7 protein (p.Leu352Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DOK7-related conditions. ClinVar contains an entry for this variant (Variation ID: 534114). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at