rs8010870

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.8928A>G(p.Leu2976Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,952 control chromosomes in the GnomAD database, including 12,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1916 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10871 hom. )

Consequence

DYNC1H1
NM_001376.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.04

Publications

24 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: Genomics England PanelApp, Orphanet, G2P
intellectual disability, autosomal dominant 13
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
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: Orphanet, Labcorp Genetics (formerly Invitae)
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DYNC1H1 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=-0.85).

BP6

Variant 14-102027424-A-G is Benign according to our data. Variant chr14-102027424-A-G is described in ClinVar as Benign. ClinVar VariationId is 128944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1H1	NM_001376.5	MANE Select	c.8928A>G	p.Leu2976Leu	synonymous	Exon 46 of 78	NP_001367.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNC1H1	ENST00000360184.10	TSL:1 MANE Select	c.8928A>G	p.Leu2976Leu	synonymous	Exon 46 of 78	ENSP00000348965.4	Q14204
DYNC1H1	ENST00000681574.1		c.8928A>G	p.Leu2976Leu	synonymous	Exon 46 of 77	ENSP00000505523.1	A0A7P0T9C4
DYNC1H1	ENST00000679720.1		c.8928A>G	p.Leu2976Leu	synonymous	Exon 46 of 78	ENSP00000505938.1	A0A7P0TA13

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22609

AN:

151960

Hom.:

1913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.138

AC:

34676

AN:

251456

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.0952

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.116

AC:

169840

AN:

1461874

Hom.:

10871

Cov.:

AF XY:

0.117

AC XY:

85244

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.228

AC:

7636

AN:

33480

American (AMR)

AF:

0.147

AC:

6588

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3829

AN:

26136

East Asian (EAS)

AF:

0.236

AC:

9358

AN:

39700

South Asian (SAS)

AF:

0.173

AC:

14901

AN:

86258

European-Finnish (FIN)

AF:

0.100

AC:

5349

AN:

53418

Middle Eastern (MID)

AF:

0.124

AC:

718

AN:

5768

European-Non Finnish (NFE)

AF:

0.102

AC:

113839

AN:

1111994

Other (OTH)

AF:

0.126

AC:

7622

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10745

21490

32236

42981

53726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4442

8884

13326

17768

22210

<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:

0.149

AC:

22632

AN:

152078

Hom.:

1916

Cov.:

AF XY:

0.148

AC XY:

10994

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.224

AC:

9290

AN:

41466

American (AMR)

AF:

0.141

AC:

2146

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

494

AN:

3472

East Asian (EAS)

AF:

0.238

AC:

1232

AN:

5168

South Asian (SAS)

AF:

0.185

AC:

889

AN:

4812

European-Finnish (FIN)

AF:

0.101

AC:

1072

AN:

10594

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7108

AN:

67988

Other (OTH)

AF:

0.156

AC:

328

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

965

1930

2894

3859

4824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.122

Hom.:

841

Bravo

AF:

0.155

Asia WGS

AF:

0.202

AC:

703

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.110

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

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

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)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.40

(source)

DANN

Benign

0.48

PhyloP100

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=82/18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over