rs201310509
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001080463.2(DYNC2H1):āc.3015A>Gā(p.Leu1005=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,609,220 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: š 0.0012 ( 0 hom., cov: 31)
Exomes š: 0.00032 ( 1 hom. )
Consequence
DYNC2H1
NM_001080463.2 synonymous
NM_001080463.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.834
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 -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 11-103152204-A-G is Benign according to our data. Variant chr11-103152204-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195571.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.834 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.3015A>G | p.Leu1005= | synonymous_variant | 21/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.3015A>G | p.Leu1005= | synonymous_variant | 21/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.3015A>G | p.Leu1005= | synonymous_variant | 21/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.3015A>G | p.Leu1005= | synonymous_variant | 21/89 | 1 | NM_001377.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00124 AC: 187AN: 151366Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000426 AC: 105AN: 246250Hom.: 0 AF XY: 0.000397 AC XY: 53AN XY: 133450
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GnomAD4 exome AF: 0.000318 AC: 463AN: 1457738Hom.: 1 Cov.: 33 AF XY: 0.000316 AC XY: 229AN XY: 724750
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GnomAD4 genome ? AF: 0.00123 AC: 187AN: 151482Hom.: 0 Cov.: 31 AF XY: 0.00126 AC XY: 93AN XY: 73944
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 10, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2021 | - - |
Jeune thoracic dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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