rs1162389472

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018051.5(DYNC2I1):c.3169G>A(p.Ala1057Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000818 in 1,589,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.434

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052066058).

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.3169G>A	p.Ala1057Thr	missense	Exon 25 of 25	NP_060521.4
DYNC2I1	NM_001350914.2		c.3031G>A	p.Ala1011Thr	missense	Exon 25 of 25	NP_001337843.1
DYNC2I1	NM_001350915.2		c.2596G>A	p.Ala866Thr	missense	Exon 24 of 24	NP_001337844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.3169G>A	p.Ala1057Thr	missense	Exon 25 of 25	ENSP00000384290.3
DYNC2I1	ENST00000444851.5	TSL:1	n.*758G>A		non_coding_transcript_exon	Exon 20 of 20	ENSP00000392608.1
DYNC2I1	ENST00000444851.5	TSL:1	n.*758G>A		3_prime_UTR	Exon 20 of 20	ENSP00000392608.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

225390

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000835

AC:

AN:

1437264

Hom.:

Cov.:

AF XY:

0.00000702

AC XY:

AN XY:

712188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32704

American (AMR)

AF:

0.00

AC:

AN:

41180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24900

East Asian (EAS)

AF:

0.00

AC:

AN:

39268

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.0000100

AC:

AN:

1098798

Other (OTH)

AF:

0.00

AC:

AN:

59218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.43

M_CAP

Benign

0.0034

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.43

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.7

REVEL

Benign

0.028

Sift

Benign

0.22

Sift4G

Benign

0.20

Polyphen

0.0060

Vest4

0.16

MutPred

0.38

Gain of disorder (P = 0.1772)

MVP

0.27

MPC

0.077

ClinPred

0.14

GERP RS

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.32

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over