rs777919963
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 3P and 10B. PM1PP2BP6_ModerateBS1BS2
The NM_001376.5(DYNC1H1):c.1390G>A(p.Asp464Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,862 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000075 ( 1 hom. )
Consequence
DYNC1H1
NM_001376.5 missense
NM_001376.5 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: 9.52
Genes affected
DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM1
In a region_of_interest Interaction with DYNC1I2 (size 255) in uniprot entity DYHC1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001376.5
PP2
Missense variant in the DYNC1H1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 122 curated pathogenic missense variants (we use a threshold of 10). The gene has 287 curated benign missense variants. Gene score misZ: 10.967 (above the threshold of 3.09). Trascript score misZ: 16.053 (above the threshold of 3.09). GenCC associations: The gene is linked to autosomal dominant non-syndromic intellectual disability, neuronopathy, distal hereditary motor, intellectual disability, autosomal dominant 13, autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures, Charcot-Marie-Tooth disease axonal type 2O.
BP6
Variant 14-101983538-G-A is Benign according to our data. Variant chr14-101983538-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472521.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000752 (11/1461862) while in subpopulation SAS AF= 0.000116 (10/86234). AF 95% confidence interval is 0.0000625. There are 1 homozygotes in gnomad4_exome. There are 4 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251326Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135882
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461862Hom.: 1 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727230
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GnomAD4 genome Cov.: 31
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31
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2O Benign:1
Jan 15, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Polyphen
P
Vest4
MutPred
Loss of glycosylation at K468 (P = 0.242);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at