11-103187397-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080463.2(DYNC2H1):c.6951C>T(p.His2317His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,612,840 control chromosomes in the GnomAD database, including 310,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31003 hom., cov: 31)

Exomes 𝑓: 0.62 ( 279605 hom. )

Consequence

DYNC2H1
NM_001080463.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.71

Publications

22 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 11-103187397-C-T is Benign according to our data. Variant chr11-103187397-C-T is described in ClinVar as Benign. ClinVar VariationId is 93529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2 link	c.6951C>T	p.His2317His	synonymous_variant	Exon 43 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3 link	c.6951C>T	p.His2317His	synonymous_variant	Exon 43 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2 link	c.6951C>T	p.His2317His	synonymous_variant	Exon 43 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7 link	c.6951C>T	p.His2317His	synonymous_variant	Exon 43 of 89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96667

AN:

151742

Hom.:

30974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.627

GnomAD2 exomes

AF:

0.637

AC:

158480

AN:

248682

AF XY:

0.630

show subpopulations

Gnomad AFR exome

AF:

0.663

Gnomad AMR exome

AF:

0.766

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.629

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.617

AC:

901343

AN:

1460980

Hom.:

279605

Cov.:

AF XY:

0.614

AC XY:

446597

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.672

AC:

22459

AN:

33444

American (AMR)

AF:

0.756

AC:

33801

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

17547

AN:

26096

East Asian (EAS)

AF:

0.503

AC:

19964

AN:

39656

South Asian (SAS)

AF:

0.557

AC:

48071

AN:

86244

European-Finnish (FIN)

AF:

0.635

AC:

33911

AN:

53398

Middle Eastern (MID)

AF:

0.651

AC:

3754

AN:

5766

European-Non Finnish (NFE)

AF:

0.616

AC:

684390

AN:

1111360

Other (OTH)

AF:

0.621

AC:

37446

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

20784

41567

62351

83134

103918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18372

36744

55116

73488

91860

<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:

0.637

AC:

96753

AN:

151860

Hom.:

31003

Cov.:

AF XY:

0.636

AC XY:

47167

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.666

AC:

27556

AN:

41404

American (AMR)

AF:

0.705

AC:

10734

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2348

AN:

3472

East Asian (EAS)

AF:

0.551

AC:

2846

AN:

5164

South Asian (SAS)

AF:

0.549

AC:

2650

AN:

4826

European-Finnish (FIN)

AF:

0.629

AC:

6643

AN:

10554

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42040

AN:

67910

Other (OTH)

AF:

0.629

AC:

1325

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1791

3582

5374

7165

8956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.633

Hom.:

18599

Bravo

AF:

0.647

Asia WGS

AF:

0.559

AC:

1944

AN:

3476

EpiCase

AF:

0.631

EpiControl

AF:

0.635

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Mar 06, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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: Frequency

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Mar 03, 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.

Asphyxiating thoracic dystrophy 3

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 12, 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.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jeune thoracic dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Short rib-polydactyly syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.4

(source)

DANN

Benign

0.40

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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