3-196296059-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152773.5(DYNLT2B):c.328C>T(p.Arg110Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,613,684 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 6 hom. )

Consequence

DYNLT2B
NM_152773.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.08

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:

ENSG00000272741 (HGNC:):

ENSG00000272741 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026103526).

BP6

Variant 3-196296059-G-A is Benign according to our data. Variant chr3-196296059-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT2B	NM_152773.5 link	c.328C>T	p.Arg110Cys	missense_variant	Exon 4 of 5	ENST00000325318.10	NP_689986.2
DYNLT2B	NM_001351628.2 link	c.328C>T	p.Arg110Cys	missense_variant	Exon 4 of 5		NP_001338557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNLT2B	ENST00000325318.10 link	c.328C>T	p.Arg110Cys	missense_variant	Exon 4 of 5	1	NM_152773.5	ENSP00000324323.5		Q8WW35
ENSG00000272741	ENST00000431391.1 link	n.317+10884C>T		intron_variant	Intron 3 of 5	5		ENSP00000405181.1		E7ESA3

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00301

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00180

AC:

452

AN:

251236

Hom.:

AF XY:

0.00193

AC XY:

262

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00280

AC:

4097

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1959

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.000787

Gnomad4 NFE exome

AF:

0.00339

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152222

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

150

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00576

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00301

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00257

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00185

AC:

225

EpiCase

AF:

0.00240

EpiControl

AF:

0.00225

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

DYNLT2B-related disorder

Benign:1

Nov 21, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.028

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-7.6

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.67

MVP

0.29

MPC

1.4

ClinPred

0.16

GERP RS

4.1

Varity_R

0.72

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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