rs12893215

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.3600A>G(p.Gln1200Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,614,008 control chromosomes in the GnomAD database, including 13,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2165 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11303 hom. )

Consequence

DYNC1H1
NM_001376.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.227

Publications

18 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, G2P, Orphanet
intellectual disability, autosomal dominant 13
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
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=-0.57).

BP6

Variant 14-101997070-A-G is Benign according to our data. Variant chr14-101997070-A-G is described in ClinVar as Benign. ClinVar VariationId is 128935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.227 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 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.3600A>G	p.Gln1200Gln	synonymous	Exon 16 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.3600A>G	p.Gln1200Gln	synonymous	Exon 16 of 78	ENSP00000348965.4	Q14204
DYNC1H1	ENST00000681574.1		c.3600A>G	p.Gln1200Gln	synonymous	Exon 16 of 77	ENSP00000505523.1	A0A7P0T9C4
DYNC1H1	ENST00000679720.1		c.3600A>G	p.Gln1200Gln	synonymous	Exon 16 of 78	ENSP00000505938.1	A0A7P0TA13

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23742

AN:

152100

Hom.:

2162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.164

GnomAD2 exomes

AF:

0.141

AC:

35376

AN:

251198

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.0958

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.118

AC:

172612

AN:

1461790

Hom.:

11303

Cov.:

AF XY:

0.119

AC XY:

86556

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.253

AC:

8479

AN:

33478

American (AMR)

AF:

0.149

AC:

6666

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

3828

AN:

26136

East Asian (EAS)

AF:

0.237

AC:

9406

AN:

39694

South Asian (SAS)

AF:

0.173

AC:

14902

AN:

86246

European-Finnish (FIN)

AF:

0.101

AC:

5396

AN:

53418

Middle Eastern (MID)

AF:

0.125

AC:

720

AN:

5766

European-Non Finnish (NFE)

AF:

0.104

AC:

115399

AN:

1111960

Other (OTH)

AF:

0.129

AC:

7816

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9300

18601

27901

37202

46502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4494

8988

13482

17976

22470

<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:

0.156

AC:

23766

AN:

152218

Hom.:

2165

Cov.:

AF XY:

0.154

AC XY:

11497

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.245

AC:

10178

AN:

41526

American (AMR)

AF:

0.145

AC:

2224

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

492

AN:

3466

East Asian (EAS)

AF:

0.239

AC:

1238

AN:

5190

South Asian (SAS)

AF:

0.185

AC:

891

AN:

4824

European-Finnish (FIN)

AF:

0.102

AC:

1084

AN:

10608

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7236

AN:

67998

Other (OTH)

AF:

0.162

AC:

343

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1026

2052

3077

4103

5129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.127

Hom.:

724

Bravo

AF:

0.164

Asia WGS

AF:

0.203

AC:

704

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.112

ClinVar

ClinVar submissions as Germline

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

-0.57

CADD

Benign

5.8

(source)

DANN

Benign

0.39

PhyloP100

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over