rs17301028
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001080463.2(DYNC2H1):c.21C>T(p.Asp7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,613,576 control chromosomes in the GnomAD database, including 7,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.065 ( 436 hom., cov: 32)
Exomes 𝑓: 0.089 ( 6608 hom. )
Consequence
DYNC2H1
NM_001080463.2 synonymous
NM_001080463.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.28
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 11-103109595-C-T is Benign according to our data. Variant chr11-103109595-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 301995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-103109595-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.28 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.21C>T | p.Asp7= | synonymous_variant | 1/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.21C>T | p.Asp7= | synonymous_variant | 1/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.21C>T | p.Asp7= | synonymous_variant | 1/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.21C>T | p.Asp7= | synonymous_variant | 1/89 | 1 | NM_001377.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0654 AC: 9955AN: 152128Hom.: 435 Cov.: 32
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GnomAD3 exomes AF: 0.0736 AC: 18308AN: 248748Hom.: 882 AF XY: 0.0776 AC XY: 10475AN XY: 134940
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GnomAD4 exome AF: 0.0892 AC: 130393AN: 1461330Hom.: 6608 Cov.: 31 AF XY: 0.0897 AC XY: 65213AN XY: 726904
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GnomAD4 genome ? AF: 0.0654 AC: 9958AN: 152246Hom.: 436 Cov.: 32 AF XY: 0.0636 AC XY: 4735AN XY: 74440
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Jeune thoracic dystrophy Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Asphyxiating thoracic dystrophy 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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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