rs752168445
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173660.5(DOK7):āc.983A>Cā(p.Gln328Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,553,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q328R) has been classified as Uncertain significance.
Frequency
Consequence
NM_173660.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.983A>C | p.Gln328Pro | missense_variant | 7/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.983A>C | p.Gln328Pro | missense_variant | 7/7 | 1 | NM_173660.5 | P1 | |
DOK7 | ENST00000643608.1 | c.551A>C | p.Gln184Pro | missense_variant | 5/8 | ||||
DOK7 | ENST00000515886.5 | c.53A>C | p.Gln18Pro | missense_variant | 4/4 | 2 | |||
DOK7 | ENST00000507039.5 | c.*204A>C | 3_prime_UTR_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.0000214 AC: 30AN: 1401208Hom.: 0 Cov.: 111 AF XY: 0.0000130 AC XY: 9AN XY: 692712
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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 | Apr 06, 2022 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 328 of the DOK7 protein (p.Gln328Pro). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 1050646). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The DOK7 p.Gln18Pro variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, MutDB, and LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs752168445) and it was also identified in control databases in 1 of 184640 chromosomes at a frequency of 0.000005 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 1 of 76350 chromosomes (freq: 0.000013), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project or the Exome Aggregation Consortium (August 8th 2016). The c.53A>C variant occurs outside the splicing consensus sequence. The p.Gln18 residue is highly conserved in mammals and other organisms. Four of five computational analyses (PolyPhen-2, SIFT, BLOSUM, and MutationTaster) suggest that the variant may impact the protein. However this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at