rs199740595
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PP2PP3_ModerateBP6BS1BS2
The NM_001376.5(DYNC1H1):c.5248G>A(p.Val1750Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000096 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1750L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001376.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.5248G>A | p.Val1750Met | missense_variant | 26/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.5248G>A | p.Val1750Met | missense_variant | 26/78 | 1 | NM_001376.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251350Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135906
GnomAD4 exome AF: 0.000103 AC: 150AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 727246
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | DYNC1H1: PP2, BS1:Supporting - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26392352, 26901136) - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2020 | 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. - |
Charcot-Marie-Tooth disease axonal type 2O Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at