3-196306939-T-A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_152773.5(DYNLT2B):c.317+4A>T variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
DYNLT2B
NM_152773.5 splice_region, intron
NM_152773.5 splice_region, intron
Scores
2
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 5.22
Genes affected
DYNLT2B (HGNC:28482): (dynein light chain Tctex-type 2B) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains. This gene encodes a subunit of the human cytoplasmic dynein-2 complex. Mutations in this gene are associated with short-rib thoracic dysplasia 17 with or without polydactyly. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 4: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai [when BayesDel_noAF, Dann was below the threshold]
PP5
Variant 3-196306939-T-A is Pathogenic according to our data. Variant chr3-196306939-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 266107.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNLT2B | ENST00000325318.10 | c.317+4A>T | splice_region_variant, intron_variant | Intron 3 of 4 | 1 | NM_152773.5 | ENSP00000324323.5 | |||
ENSG00000272741 | ENST00000431391.1 | n.317+4A>T | splice_region_variant, intron_variant | Intron 3 of 5 | 5 | ENSP00000405181.1 | ||||
DYNLT2B | ENST00000426563.5 | n.*183+4A>T | splice_region_variant, intron_variant | Intron 3 of 4 | 2 | ENSP00000415835.1 | ||||
DYNLT2B | ENST00000446494.1 | n.317+4A>T | splice_region_variant, intron_variant | Intron 3 of 5 | 3 | ENSP00000410605.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Short-rib thoracic dysplasia 17 with or without polydactyly Pathogenic:1
Mar 14, 2024
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Asphyxiating thoracic dystrophy 3 Pathogenic:1
-
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 17
DS_DL_spliceai
Position offset: 4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at