rs192003811
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_001080463.2(DYNC2H1):āc.9960T>Cā(p.Ala3320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,544,904 control chromosomes in the GnomAD database, including 25 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 0.0032 ( 0 hom., cov: 32)
Exomes š: 0.0048 ( 25 hom. )
Consequence
DYNC2H1
NM_001080463.2 synonymous
NM_001080463.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.08
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 11-103245271-T-C is Benign according to our data. Variant chr11-103245271-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 302084.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Likely_benign=3, Uncertain_significance=1}. Variant chr11-103245271-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.08 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 25 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.9960T>C | p.Ala3320= | synonymous_variant | 66/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.9939T>C | p.Ala3313= | synonymous_variant | 65/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.9960T>C | p.Ala3320= | synonymous_variant | 66/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.9939T>C | p.Ala3313= | synonymous_variant | 65/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000334267.11 | c.2205+110852T>C | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00318 AC: 484AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00271 AC: 428AN: 157898Hom.: 2 AF XY: 0.00267 AC XY: 222AN XY: 83080
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GnomAD4 exome AF: 0.00482 AC: 6707AN: 1392668Hom.: 25 Cov.: 29 AF XY: 0.00479 AC XY: 3291AN XY: 686982
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GnomAD4 genome ? AF: 0.00319 AC: 485AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00278 AC XY: 207AN XY: 74428
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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
Jeune thoracic dystrophy Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 12, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 13, 2017 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | DYNC2H1: BP4 - |
Asphyxiating thoracic dystrophy 3 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely 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