11-103186319-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377.3(DYNC2H1):c.6711A>G(p.Arg2237Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,612,044 control chromosomes in the GnomAD database, including 302,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R2237R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.60 ( 27305 hom., cov: 30)

Exomes 𝑓: 0.61 ( 275479 hom. )

Consequence

DYNC2H1
NM_001377.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.276

Publications

21 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), Ambry Genetics, Orphanet, G2P, ClinGen
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-103186319-A-G is Benign according to our data. Variant chr11-103186319-A-G is described in ClinVar as Benign. ClinVar VariationId is 302056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.276 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	NM_001080463.2	MANE Plus Clinical	c.6711A>G	p.Arg2237Arg	synonymous	Exon 42 of 90	NP_001073932.1	Q8NCM8-2
	DYNC2H1	NM_001377.3	MANE Select	c.6711A>G	p.Arg2237Arg	synonymous	Exon 42 of 89	NP_001368.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNC2H1	ENST00000650373.2	MANE Plus Clinical	c.6711A>G	p.Arg2237Arg	synonymous	Exon 42 of 90	ENSP00000497174.1	Q8NCM8-2
DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.6711A>G	p.Arg2237Arg	synonymous	Exon 42 of 89	ENSP00000364887.2	Q8NCM8-1
DYNC2H1	ENST00000334267.11	TSL:1	c.2205+51900A>G		intron	N/A	ENSP00000334021.7	Q8NCM8-3

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90442

AN:

151500

Hom.:

27276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.675

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.546

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.659

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.597

GnomAD2 exomes

AF:

0.627

AC:

155479

AN:

248044

AF XY:

0.622

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.631

Gnomad NFE exome

AF:

0.628

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.612

AC:

894337

AN:

1460426

Hom.:

275479

Cov.:

AF XY:

0.611

AC XY:

443527

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.525

AC:

17555

AN:

33438

American (AMR)

AF:

0.750

AC:

33462

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

17518

AN:

26080

East Asian (EAS)

AF:

0.504

AC:

19954

AN:

39618

South Asian (SAS)

AF:

0.557

AC:

48017

AN:

86226

European-Finnish (FIN)

AF:

0.628

AC:

33487

AN:

53310

Middle Eastern (MID)

AF:

0.640

AC:

3687

AN:

5764

European-Non Finnish (NFE)

AF:

0.615

AC:

683849

AN:

1111076

Other (OTH)

AF:

0.610

AC:

36808

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

20159

40318

60476

80635

100794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18332

36664

54996

73328

91660

<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:

0.597

AC:

90515

AN:

151618

Hom.:

27305

Cov.:

AF XY:

0.597

AC XY:

44218

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.528

AC:

21824

AN:

41352

American (AMR)

AF:

0.694

AC:

10538

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.675

AC:

2338

AN:

3462

East Asian (EAS)

AF:

0.552

AC:

2835

AN:

5134

South Asian (SAS)

AF:

0.547

AC:

2629

AN:

4804

European-Finnish (FIN)

AF:

0.622

AC:

6559

AN:

10542

Middle Eastern (MID)

AF:

0.661

AC:

193

AN:

292

European-Non Finnish (NFE)

AF:

0.618

AC:

41918

AN:

67826

Other (OTH)

AF:

0.600

AC:

1264

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1834

3667

5501

7334

9168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.612

Hom.:

17622

Bravo

AF:

0.601

EpiCase

AF:

0.631

EpiControl

AF:

0.635

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Asphyxiating thoracic dystrophy 3 (2)

Jeune thoracic dystrophy (1)

not provided (1)

Short rib-polydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.68

(source)

DANN

Benign

0.35

PhyloP100

-0.28

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

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