3-196306939-T-A

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

Scores

2
Splicing: ADA: 0.9999
2

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 5.22
Variant links:
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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYNLT2BNM_152773.5 linkc.317+4A>T splice_region_variant, intron_variant Intron 3 of 4 ENST00000325318.10 NP_689986.2
DYNLT2BNM_001351628.2 linkc.317+4A>T splice_region_variant, intron_variant Intron 3 of 4 NP_001338557.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNLT2BENST00000325318.10 linkc.317+4A>T splice_region_variant, intron_variant Intron 3 of 4 1 NM_152773.5 ENSP00000324323.5 Q8WW35
ENSG00000272741ENST00000431391.1 linkn.317+4A>T splice_region_variant, intron_variant Intron 3 of 5 5 ENSP00000405181.1 E7ESA3
DYNLT2BENST00000426563.5 linkn.*183+4A>T splice_region_variant, intron_variant Intron 3 of 4 2 ENSP00000415835.1 F8WD40
DYNLT2BENST00000446494.1 linkn.317+4A>T splice_region_variant, intron_variant Intron 3 of 5 3 ENSP00000410605.1 E7ER86

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
29
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
26
DANN
Benign
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.95
SpliceAI score (max)
0.96
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.54
Position offset: 17
DS_DL_spliceai
0.96
Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886039815; hg19: chr3-196033810; API