rs118191062
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001080463.2(DYNC2H1):āc.3660T>Cā(p.Pro1220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,612,412 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.015 ( 30 hom., cov: 32)
Exomes š: 0.022 ( 431 hom. )
Consequence
DYNC2H1
NM_001080463.2 synonymous
NM_001080463.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.124
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 11-103155417-T-C is Benign according to our data. Variant chr11-103155417-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 302028.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}. Variant chr11-103155417-T-C is described in Lovd as [Likely_benign]. Variant chr11-103155417-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.124 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0153 (2329/152062) while in subpopulation NFE AF= 0.024 (1626/67882). AF 95% confidence interval is 0.023. There are 30 homozygotes in gnomad4. There are 1127 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 30 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.3660T>C | p.Pro1220= | synonymous_variant | 25/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.3660T>C | p.Pro1220= | synonymous_variant | 25/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.3660T>C | p.Pro1220= | synonymous_variant | 25/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.3660T>C | p.Pro1220= | synonymous_variant | 25/89 | 1 | NM_001377.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0153 AC: 2328AN: 151948Hom.: 30 Cov.: 32
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GnomAD3 exomes AF: 0.0164 AC: 4068AN: 247908Hom.: 58 AF XY: 0.0163 AC XY: 2193AN XY: 134518
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GnomAD4 exome AF: 0.0221 AC: 32273AN: 1460350Hom.: 431 Cov.: 34 AF XY: 0.0215 AC XY: 15621AN XY: 726440
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GnomAD4 genome ? AF: 0.0153 AC: 2329AN: 152062Hom.: 30 Cov.: 32 AF XY: 0.0152 AC XY: 1127AN XY: 74358
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 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. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Asphyxiating thoracic dystrophy 3 Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 19, 2023 | - - |
Short rib-polydactyly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Jeune thoracic dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
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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