rs761695197
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM1PP2BP4_ModerateBP6BS2
The NM_001376.5(DYNC1H1):c.4510G>A(p.Val1504Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V1504V) has been classified as Likely benign.
Frequency
Consequence
NM_001376.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.4510G>A | p.Val1504Ile | missense_variant | 21/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.4510G>A | p.Val1504Ile | missense_variant | 21/78 | 1 | NM_001376.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251472Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135918
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461880Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727244
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures;C3280220:Charcot-Marie-Tooth disease axonal type 2O;C3281202:Intellectual disability, autosomal dominant 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Feb 11, 2022 | This variant has not been reported in the literature but is present in 0.07% (8/10370) of Ashkenazi Jewish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14 102467986 G A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:246361). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Charcot-Marie-Tooth disease axonal type 2O Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2019 | - - |
DYNC1H1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 05, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at