rs771511132
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_001080463.2(DYNC2H1):c.625T>A(p.Phe209Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000063 in 1,570,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
DYNC2H1
NM_001080463.2 missense
NM_001080463.2 missense
Scores
1
6
6
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-103116573-T-A is Pathogenic according to our data. Variant chr11-103116573-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446586.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.625T>A | p.Phe209Ile | missense_variant | 5/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.625T>A | p.Phe209Ile | missense_variant | 5/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.625T>A | p.Phe209Ile | missense_variant | 5/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.625T>A | p.Phe209Ile | missense_variant | 5/89 | 1 | NM_001377.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 151814Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000134 AC: 3AN: 223852Hom.: 0 AF XY: 0.00000821 AC XY: 1AN XY: 121868
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GnomAD4 exome AF: 0.0000649 AC: 92AN: 1418650Hom.: 0 Cov.: 30 AF XY: 0.0000610 AC XY: 43AN XY: 704384
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GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 151814Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74128
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:4
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Asphyxiating thoracic dystrophy 3 Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Polyphen
0.20, 0.87, 0.098
.;B;P;B;B;B
Vest4
0.70, 0.70, 0.70
MutPred
Gain of catalytic residue at F209 (P = 0.013);Gain of catalytic residue at F209 (P = 0.013);Gain of catalytic residue at F209 (P = 0.013);Gain of catalytic residue at F209 (P = 0.013);Gain of catalytic residue at F209 (P = 0.013);Gain of catalytic residue at F209 (P = 0.013);
MVP
0.70
MPC
0.088
ClinPred
D
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