chr11-103155510-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_001080463.2(DYNC2H1):c.3744+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,599,350 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00091 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
DYNC2H1
NM_001080463.2 intron
NM_001080463.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0290
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 Benign. Variant got -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 11-103155510-C-T is Benign according to our data. Variant chr11-103155510-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 281763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.3744+9C>T | intron_variant | ENST00000650373.2 | |||
DYNC2H1 | NM_001377.3 | c.3744+9C>T | intron_variant | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000375735.7 | c.3744+9C>T | intron_variant | 1 | NM_001377.3 | P3 | |||
DYNC2H1 | ENST00000650373.2 | c.3744+9C>T | intron_variant | NM_001080463.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000901 AC: 137AN: 152004Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000187 AC: 44AN: 235592Hom.: 0 AF XY: 0.000117 AC XY: 15AN XY: 127870
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GnomAD4 exome AF: 0.0000656 AC: 95AN: 1447228Hom.: 0 Cov.: 33 AF XY: 0.0000528 AC XY: 38AN XY: 719314
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GnomAD4 genome AF: 0.000914 AC: 139AN: 152122Hom.: 1 Cov.: 32 AF XY: 0.000901 AC XY: 67AN XY: 74364
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 17, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 28, 2015 | - - |
Jeune thoracic dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
DYNC2H1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 04, 2019 | 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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