rs376892534
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_001080463.2(DYNC2H1):c.6478-16G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,456,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
DYNC2H1
NM_001080463.2 splice_polypyrimidine_tract, intron
NM_001080463.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.769
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 11-103184880-G-A is Pathogenic according to our data. Variant chr11-103184880-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 558752.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.6478-16G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000650373.2 | |||
DYNC2H1 | NM_001377.3 | c.6478-16G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000375735.7 | c.6478-16G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001377.3 | P3 | |||
DYNC2H1 | ENST00000650373.2 | c.6478-16G>A | splice_polypyrimidine_tract_variant, intron_variant | NM_001080463.2 | A1 | ||||
DYNC2H1 | ENST00000334267.11 | c.2205+50461G>A | intron_variant | 1 | |||||
DYNC2H1 | ENST00000649323.1 | c.*4023-16G>A | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247562Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134308
GnomAD3 exomes
AF:
AC:
2
AN:
247562
Hom.:
AF XY:
AC XY:
1
AN XY:
134308
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000892 AC: 13AN: 1456730Hom.: 0 Cov.: 30 AF XY: 0.00000828 AC XY: 6AN XY: 724612
GnomAD4 exome
AF:
AC:
13
AN:
1456730
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
724612
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Rare Disease Group, Clinical Genetics, Karolinska Institutet | May 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: 16
Find out detailed SpliceAI scores and Pangolin per-transcript scores at