3-196306971-T-A

Position:

chr3-196306971-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000325318.10(DYNLT2B):c.289A>T(p.Ile97Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00025 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

DYNLT2B
ENST00000325318.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLT2B	NM_152773.5 linkuse as main transcript	c.289A>T	p.Ile97Phe	missense_variant	3/5	ENST00000325318.10	NP_689986.2
DYNLT2B	NM_001351628.2 linkuse as main transcript	c.289A>T	p.Ile97Phe	missense_variant	3/5		NP_001338557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DYNLT2B	ENST00000325318.10 linkuse as main transcript	c.289A>T	p.Ile97Phe	missense_variant	3/5	1	NM_152773.5	ENSP00000324323	P1
DYNLT2B	ENST00000446494.1 linkuse as main transcript	c.289A>T	p.Ile97Phe	missense_variant, NMD_transcript_variant	3/6	3		ENSP00000410605
DYNLT2B	ENST00000426563.5 linkuse as main transcript	c.*155A>T		3_prime_UTR_variant, NMD_transcript_variant	3/5	2		ENSP00000415835

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000282

AC:

AN:

251356

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000261

AC:

381

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

187

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000144

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 18, 2022

This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 97 of the TCTEX1D2 protein (p.Ile97Phe). This variant is present in population databases (rs147435808, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TCTEX1D2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.54

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.94

MVP

0.65

MPC

1.5

ClinPred

0.36

GERP RS

5.3

Varity_R

0.46

gMVP

0.80

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over