chr7-158879928-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018051.5(DYNC2I1):c.818A>G(p.Gln273Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,610,718 control chromosomes in the GnomAD database, including 136,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18990 hom., cov: 33)

Exomes 𝑓: 0.39 ( 117187 hom. )

Consequence

DYNC2I1
NM_018051.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.177

Publications

48 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2566614E-6).

BP6

Variant 7-158879928-A-G is Benign according to our data. Variant chr7-158879928-A-G is described in ClinVar as Benign. ClinVar VariationId is 516219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2I1	NM_018051.5 link	c.818A>G	p.Gln273Arg	missense_variant	Exon 5 of 25	ENST00000407559.8	NP_060521.4	Q8WVS4A0A140VK66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8 link	c.818A>G	p.Gln273Arg	missense_variant	Exon 5 of 25	1	NM_018051.5	ENSP00000384290.3		Q8WVS4
DYNC2I1	ENST00000444851.5 link	n.149A>G		non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000392608.1		H7C022

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72760

AN:

151986

Hom.:

18949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.457

GnomAD2 exomes

AF:

0.439

AC:

107989

AN:

245938

AF XY:

0.438

show subpopulations

Gnomad AFR exome

AF:

0.687

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.713

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.392

AC:

571881

AN:

1458614

Hom.:

117187

Cov.:

AF XY:

0.395

AC XY:

286394

AN XY:

725872

show subpopulations

African (AFR)

AF:

0.689

AC:

22725

AN:

32980

American (AMR)

AF:

0.428

AC:

18680

AN:

43662

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

9056

AN:

26004

East Asian (EAS)

AF:

0.700

AC:

27770

AN:

39680

South Asian (SAS)

AF:

0.512

AC:

44005

AN:

86014

European-Finnish (FIN)

AF:

0.378

AC:

20120

AN:

53282

Middle Eastern (MID)

AF:

0.465

AC:

2670

AN:

5738

European-Non Finnish (NFE)

AF:

0.362

AC:

402097

AN:

1111090

Other (OTH)

AF:

0.412

AC:

24758

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

19399

38799

58198

77598

96997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13030

26060

39090

52120

65150

<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:

0.479

AC:

72857

AN:

152104

Hom.:

18990

Cov.:

AF XY:

0.485

AC XY:

36049

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.679

AC:

28169

AN:

41476

American (AMR)

AF:

0.457

AC:

6980

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1207

AN:

3472

East Asian (EAS)

AF:

0.722

AC:

3741

AN:

5180

South Asian (SAS)

AF:

0.527

AC:

2542

AN:

4826

European-Finnish (FIN)

AF:

0.374

AC:

3962

AN:

10586

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24817

AN:

67992

Other (OTH)

AF:

0.456

AC:

963

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1837

3675

5512

7350

9187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.400

Hom.:

65581

Bravo

AF:

0.490

TwinsUK

AF:

0.373

AC:

1382

ALSPAC

AF:

0.363

AC:

1399

ESP6500AA

AF:

0.653

AC:

2463

ESP6500EA

AF:

0.367

AC:

3004

ExAC

AF:

0.441

AC:

53237

Asia WGS

AF:

0.605

AC:

2101

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Short-rib thoracic dysplasia 8 with or without polydactyly

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 13, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.18

(source)

DANN

Benign

0.12

DEOGEN2

Benign

0.00067

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.97

PhyloP100

0.18

PrimateAI

Benign

0.25

PROVEAN

Benign

1.4

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.014

MPC

0.085

ClinPred

0.00069

GERP RS

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.034

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over