rs187451323
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_001080463.2(DYNC2H1):c.10866G>A(p.Pro3622=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,608,416 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
DYNC2H1
NM_001080463.2 synonymous
NM_001080463.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.00
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 11-103283040-G-A is Benign according to our data. Variant chr11-103283040-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 302097.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2, Benign=1}.
BP7
?
Synonymous conserved (PhyloP=-2 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.10866G>A | p.Pro3622= | synonymous_variant | 74/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.10845G>A | p.Pro3615= | synonymous_variant | 73/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.10866G>A | p.Pro3622= | synonymous_variant | 74/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.10845G>A | p.Pro3615= | synonymous_variant | 73/89 | 1 | NM_001377.3 | P3 | |
ENST00000649070.1 | n.690+9976C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000770 AC: 117AN: 151988Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000264 AC: 65AN: 246644Hom.: 0 AF XY: 0.000224 AC XY: 30AN XY: 133926
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GnomAD4 exome AF: 0.000126 AC: 183AN: 1456308Hom.: 1 Cov.: 30 AF XY: 0.000120 AC XY: 87AN XY: 724044
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GnomAD4 genome ? AF: 0.000769 AC: 117AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.000699 AC XY: 52AN XY: 74354
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Uncertain:1Benign:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 09, 2021 | - - |
Short rib-polydactyly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Jeune thoracic dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
DYNC2H1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 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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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