rs11225584

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001080463.2(DYNC2H1):c.6420T>C(p.Asn2140Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,595,920 control chromosomes in the GnomAD database, including 11,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1019 hom., cov: 31)

Exomes 𝑓: 0.12 ( 10595 hom. )

Consequence

DYNC2H1
NM_001080463.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.330

Publications

15 publications found

Variant links:

Genes affected

DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

DYNC2H1 Gene-Disease associations (from GenCC):

asphyxiating thoracic dystrophy 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Majewski type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Verma-Naumoff type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYNC2H1 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 (BayesDel_noAF=-0.53).

BP6

Variant 11-103181829-T-C is Benign according to our data. Variant chr11-103181829-T-C is described in ClinVar as Benign. ClinVar VariationId is 302054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 link	c.6420T>C	p.Asn2140Asn	synonymous_variant	Exon 40 of 90	ENST00000650373.2	NP_001073932.1	Q8NCM8-2
DYNC2H1	NM_001377.3 link	c.6420T>C	p.Asn2140Asn	synonymous_variant	Exon 40 of 89	ENST00000375735.7	NP_001368.2	Q8NCM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 link	c.6420T>C	p.Asn2140Asn	synonymous_variant	Exon 40 of 90		NM_001080463.2	ENSP00000497174.1		Q8NCM8-2
DYNC2H1	ENST00000375735.7 link	c.6420T>C	p.Asn2140Asn	synonymous_variant	Exon 40 of 89	1	NM_001377.3	ENSP00000364887.2		Q8NCM8-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16337

AN:

151578

Hom.:

1016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0766

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.0829

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.115

AC:

26097

AN:

226062

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.0784

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.117

AC:

169540

AN:

1444224

Hom.:

10595

Cov.:

AF XY:

0.119

AC XY:

85352

AN XY:

717004

show subpopulations

African (AFR)

AF:

0.0742

AC:

2452

AN:

33060

American (AMR)

AF:

0.0575

AC:

2463

AN:

42842

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2837

AN:

25750

East Asian (EAS)

AF:

0.217

AC:

8481

AN:

39036

South Asian (SAS)

AF:

0.160

AC:

13364

AN:

83598

European-Finnish (FIN)

AF:

0.133

AC:

6997

AN:

52550

Middle Eastern (MID)

AF:

0.0678

AC:

385

AN:

5676

European-Non Finnish (NFE)

AF:

0.114

AC:

125616

AN:

1102144

Other (OTH)

AF:

0.117

AC:

6945

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7512

15024

22535

30047

37559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4690

9380

14070

18760

23450

<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:

0.108

AC:

16359

AN:

151696

Hom.:

1019

Cov.:

AF XY:

0.109

AC XY:

8093

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.0770

AC:

3196

AN:

41498

American (AMR)

AF:

0.0826

AC:

1255

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

379

AN:

3464

East Asian (EAS)

AF:

0.214

AC:

1110

AN:

5178

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4818

European-Finnish (FIN)

AF:

0.134

AC:

1416

AN:

10572

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7742

AN:

67674

Other (OTH)

AF:

0.103

AC:

216

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

736

1472

2209

2945

3681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.111

Hom.:

3027

Bravo

AF:

0.101

Asia WGS

AF:

0.165

AC:

575

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Apr 22, 2016

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. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jeune thoracic dystrophy

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

- -

Asphyxiating thoracic dystrophy 3

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.8

(source)

DANN

Benign

0.46

PhyloP100

0.33

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