Genetic Variant DYNLT2B:p.Ile97Val (chr3-196306971-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152773.5(DYNLT2B):c.289A>G(p.Ile97Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I97F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

DYNLT2B
NM_152773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.68

Publications

0 publications found

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]

DYNLT2B Gene-Disease associations (from GenCC):

short-rib thoracic dysplasia 17 with or without polydactyly
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

DYNLT2B links:

ENSG00000272741 (HGNC:):

ENSG00000272741 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41112614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	NM_152773.5	MANE Select	c.289A>G	p.Ile97Val	missense	Exon 3 of 5	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.289A>G	p.Ile97Val	missense	Exon 3 of 5	NP_001338557.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNLT2B	ENST00000325318.10	TSL:1 MANE Select	c.289A>G	p.Ile97Val	missense	Exon 3 of 5	ENSP00000324323.5	Q8WW35
ENSG00000272741	ENST00000431391.1	TSL:5	n.289A>G		non_coding_transcript_exon	Exon 3 of 6	ENSP00000405181.1	E7ESA3
DYNLT2B	ENST00000931284.1		c.289A>G	p.Ile97Val	missense	Exon 3 of 6	ENSP00000601343.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0082

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.7

PhyloP100

3.7

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.96

REVEL

Benign

0.17

Sift

Benign

0.052

Sift4G

Uncertain

0.012

Polyphen

0.85

Vest4

0.45

MutPred

0.68

Gain of sheet (P = 0.1208)

MVP

0.34

MPC

0.87

ClinPred

0.85

GERP RS

5.3

Varity_R

0.13

gMVP

0.48

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over