NM_016008.4:c.98T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016008.4(DYNC2LI1):c.98T>C(p.Phe33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,594,682 control chromosomes in the GnomAD database, including 136,513 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.50 ( 22438 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114075 hom. )

Consequence

DYNC2LI1
NM_016008.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

DYNC2LI1 (HGNC:24595): (dynein cytoplasmic 2 light intermediate chain 1) This gene encodes a protein that is a component of the dynein-2 microtubule motor protein complex that plays a role in the retrograde transport of cargo in primary cilia via the intraflagellar transport system. This gene is ubiquitously expressed and its protein, which localizes to the axoneme and Golgi apparatus, interacts directly with the cytoplasmic dynein 2 heavy chain 1 protein to form part of the multi-protein dynein-2 complex. Mutations in this gene produce defects in the dynein-2 complex which result in several types of ciliopathy including short-rib thoracic dysplasia 15 with polydactyly (SRTD15). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

DYNC2LI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.595019E-7).

BP6

Variant 2-43776871-T-C is Benign according to our data. Variant chr2-43776871-T-C is described in ClinVar as [Benign]. Clinvar id is 1255528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2LI1	NM_016008.4 link	c.98T>C	p.Phe33Ser	missense_variant	Exon 2 of 13	ENST00000260605.12	NP_057092.2	Q8TCX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2LI1	ENST00000260605.12 link	c.98T>C	p.Phe33Ser	missense_variant	Exon 2 of 13	1	NM_016008.4	ENSP00000260605.8		Q8TCX1-1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76067

AN:

151950

Hom.:

22372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.423

AC:

103053

AN:

243646

Hom.:

24286

AF XY:

0.418

AC XY:

55098

AN XY:

131732

show subpopulations

Gnomad AFR exome

AF:

0.836

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.385

AC:

555749

AN:

1442614

Hom.:

114075

Cov.:

AF XY:

0.388

AC XY:

278609

AN XY:

718068

show subpopulations

Gnomad4 AFR exome

AF:

0.846

Gnomad4 AMR exome

AF:

0.509

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.525

Gnomad4 FIN exome

AF:

0.347

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.400

GnomAD4 genome

AF:

0.501

AC:

76189

AN:

152068

Hom.:

22438

Cov.:

AF XY:

0.498

AC XY:

36980

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.824

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.385

Hom.:

22270

Bravo

AF:

0.524

TwinsUK

AF:

0.363

AC:

1345

ALSPAC

AF:

0.362

AC:

1397

ESP6500AA

AF:

0.818

AC:

3602

ESP6500EA

AF:

0.365

AC:

3138

ExAC

AF:

0.436

AC:

52910

Asia WGS

AF:

0.385

AC:

1343

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Short-rib thoracic dysplasia 15 with polydactyly

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.015

T;.;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.24

T;T;T;T

MetaRNN

Benign

6.6e-7

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.7

N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.8

N;N;N;.

REVEL

Benign

0.27

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.12

MPC

0.056

ClinPred

0.011

GERP RS

5.4

Varity_R

0.25

gMVP

0.34

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