rs13749

Variant names:

Variant summary

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

The NM_001376.5(DYNC1H1):c.13080T>C(p.Thr4360Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,124 control chromosomes in the GnomAD database, including 38,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 9246 hom., cov: 29)

Exomes 𝑓: 0.18 ( 29237 hom. )

Consequence

DYNC1H1
NM_001376.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -2.08

Publications

25 publications found

Variant links:

Genes affected

DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]

DYNC1H1 Gene-Disease associations (from GenCC):

autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp
intellectual disability, autosomal dominant 13
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
neuronopathy, distal hereditary motor
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease axonal type 2O
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DYNC1H1 links:

ENSG00000293472 (HGNC:):

ENSG00000293472 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=-0.81).

BP6

Variant 14-102047890-T-C is Benign according to our data. Variant chr14-102047890-T-C is described in ClinVar as Benign. ClinVar VariationId is 128929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1H1	NM_001376.5	MANE Select	c.13080T>C	p.Thr4360Thr	synonymous	Exon 73 of 78	NP_001367.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNC1H1	ENST00000360184.10	TSL:1 MANE Select	c.13080T>C	p.Thr4360Thr	synonymous	Exon 73 of 78	ENSP00000348965.4
DYNC1H1	ENST00000681574.1		c.13080T>C	p.Thr4360Thr	synonymous	Exon 73 of 77	ENSP00000505523.1
DYNC1H1	ENST00000679720.1		c.13080T>C	p.Thr4360Thr	synonymous	Exon 73 of 78	ENSP00000505938.1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44567

AN:

151360

Hom.:

9216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.590

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.225

AC:

56385

AN:

251050

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.597

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.183

AC:

267168

AN:

1461646

Hom.:

29237

Cov.:

AF XY:

0.184

AC XY:

133540

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.616

AC:

20616

AN:

33480

American (AMR)

AF:

0.255

AC:

11388

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6364

AN:

26136

East Asian (EAS)

AF:

0.270

AC:

10737

AN:

39698

South Asian (SAS)

AF:

0.256

AC:

22118

AN:

86258

European-Finnish (FIN)

AF:

0.131

AC:

6967

AN:

53192

Middle Eastern (MID)

AF:

0.278

AC:

1604

AN:

5768

European-Non Finnish (NFE)

AF:

0.157

AC:

174584

AN:

1112002

Other (OTH)

AF:

0.212

AC:

12790

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

13444

26887

40331

53774

67218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6610

13220

19830

26440

33050

<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:

0.295

AC:

44657

AN:

151478

Hom.:

9246

Cov.:

AF XY:

0.290

AC XY:

21458

AN XY:

74068

show subpopulations

African (AFR)

AF:

0.590

AC:

24265

AN:

41126

American (AMR)

AF:

0.256

AC:

3883

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

800

AN:

3464

East Asian (EAS)

AF:

0.275

AC:

1412

AN:

5140

South Asian (SAS)

AF:

0.269

AC:

1291

AN:

4808

European-Finnish (FIN)

AF:

0.128

AC:

1348

AN:

10528

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10914

AN:

67914

Other (OTH)

AF:

0.285

AC:

599

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1144

2289

3433

4578

5722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.207

Hom.:

9869

Bravo

AF:

0.319

Asia WGS

AF:

0.281

AC:

975

AN:

3478

EpiCase

AF:

0.178

EpiControl

AF:

0.178

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Charcot-Marie-Tooth disease axonal type 2O (3)

not provided (2)

Autosomal dominant cerebellar ataxia (1)

Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures (1)

Charcot-Marie-Tooth disease (1)

Inborn genetic diseases (1)

Intellectual disability, autosomal dominant 13 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.016

(source)

DANN

Benign

0.48

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over