NM_018051.5:c.445C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018051.5(DYNC2I1):c.445C>T(p.Arg149Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,545,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.190

Publications

0 publications found

Variant links:

Genes affected

DYNC2I1 (HGNC:21862): (dynein 2 intermediate chain 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) and may facilitate the formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes. [provided by RefSeq, Mar 2014]

DYNC2I1 Gene-Disease associations (from GenCC):

short-rib thoracic dysplasia 8 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Verma-Naumoff type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYNC2I1 links:

ENSG00000296853 (HGNC:):

ENSG00000296853 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09137884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018051.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNC2I1	NM_018051.5	MANE Select	c.445C>T	p.Arg149Cys	missense	Exon 3 of 25	NP_060521.4
DYNC2I1	NM_001350915.2		c.-73C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 24	NP_001337844.1
DYNC2I1	NM_001350917.2		c.-922C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 26	NP_001337846.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.445C>T	p.Arg149Cys	missense	Exon 3 of 25	ENSP00000384290.3
DYNC2I1	ENST00000860814.1		c.445C>T	p.Arg149Cys	missense	Exon 3 of 26	ENSP00000530873.1
DYNC2I1	ENST00000961351.1		c.445C>T	p.Arg149Cys	missense	Exon 3 of 26	ENSP00000631410.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000210

AC:

AN:

142722

AF XY:

0.0000130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000820

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1393326

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

687268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31464

American (AMR)

AF:

0.000112

AC:

AN:

35596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4872

European-Non Finnish (NFE)

AF:

0.0000278

AC:

AN:

1078748

Other (OTH)

AF:

0.000156

AC:

AN:

57820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Short-rib thoracic dysplasia 8 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.59

M_CAP

Benign

0.013

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.19

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.079

Sift

Benign

0.076

Sift4G

Pathogenic

0.0010

Polyphen

0.013

Vest4

0.17

MutPred

0.35

Loss of MoRF binding (P = 0.0055)

MVP

0.35

MPC

0.48

ClinPred

0.24

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.019

Mutation Taster

=95/5

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over