14-102015282-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001376.5(DYNC1H1):c.7192C>T(p.Arg2398Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00021 in 1,614,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. R2398H) has been classified as Likely benign.
Frequency
Consequence
NM_001376.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.7192C>T | p.Arg2398Cys | missense_variant | 35/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.7192C>T | p.Arg2398Cys | missense_variant | 35/78 | 1 | NM_001376.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000362 AC: 91AN: 251118Hom.: 0 AF XY: 0.000353 AC XY: 48AN XY: 135786
GnomAD4 exome AF: 0.000202 AC: 296AN: 1461860Hom.: 1 Cov.: 31 AF XY: 0.000191 AC XY: 139AN XY: 727226
GnomAD4 genome AF: 0.000283 AC: 43AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | DYNC1H1: PP2, BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 10, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 09, 2020 | This variant is associated with the following publications: (PMID: 26100331, 23891399) - |
Charcot-Marie-Tooth disease axonal type 2O Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 30, 2016 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2020 | This alteration is classified as 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. - |
Autosomal dominant cerebellar ataxia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at