14-102038501-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_001376.5(DYNC1H1):c.10950C>T(p.Asn3650Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 1,614,040 control chromosomes in the GnomAD database, including 4,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 325 hom., cov: 32)

Exomes 𝑓: 0.069 ( 3820 hom. )

Consequence

DYNC1H1
NM_001376.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 3.05

Publications

9 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:

ENSG00000293472 (HGNC:):

ENSG00000293472 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=-0.25).

BP6

Variant 14-102038501-C-T is Benign according to our data. Variant chr14-102038501-C-T is described in ClinVar as Benign. ClinVar VariationId is 128927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 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.10950C>T	p.Asn3650Asn	synonymous	Exon 58 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.10950C>T	p.Asn3650Asn	synonymous	Exon 58 of 78	ENSP00000348965.4	Q14204
DYNC1H1	ENST00000681574.1		c.10950C>T	p.Asn3650Asn	synonymous	Exon 58 of 77	ENSP00000505523.1	A0A7P0T9C4
DYNC1H1	ENST00000679720.1		c.10950C>T	p.Asn3650Asn	synonymous	Exon 58 of 78	ENSP00000505938.1	A0A7P0TA13

Frequencies

GnomAD3 genomes

AF:

0.0609

AC:

9258

AN:

152064

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0417

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.0816

Gnomad EAS

AF:

0.00713

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0954

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0676

GnomAD2 exomes

AF:

0.0676

AC:

16988

AN:

251386

AF XY:

0.0712

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0798

Gnomad EAS exome

AF:

0.00984

Gnomad FIN exome

AF:

0.0894

Gnomad NFE exome

AF:

0.0707

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0692

AC:

101090

AN:

1461858

Hom.:

3820

Cov.:

AF XY:

0.0712

AC XY:

51750

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0438

AC:

1467

AN:

33480

American (AMR)

AF:

0.0393

AC:

1757

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0799

AC:

2087

AN:

26134

East Asian (EAS)

AF:

0.00788

AC:

313

AN:

39698

South Asian (SAS)

AF:

0.123

AC:

10643

AN:

86250

European-Finnish (FIN)

AF:

0.0937

AC:

5006

AN:

53414

Middle Eastern (MID)

AF:

0.0751

AC:

433

AN:

5766

European-Non Finnish (NFE)

AF:

0.0678

AC:

75362

AN:

1112002

Other (OTH)

AF:

0.0666

AC:

4022

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6869

13738

20606

27475

34344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2822

5644

8466

11288

14110

<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:

0.0609

AC:

9263

AN:

152182

Hom.:

325

Cov.:

AF XY:

0.0617

AC XY:

4591

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0418

AC:

1734

AN:

41528

American (AMR)

AF:

0.0459

AC:

701

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0816

AC:

283

AN:

3470

East Asian (EAS)

AF:

0.00714

AC:

AN:

5180

South Asian (SAS)

AF:

0.128

AC:

616

AN:

4816

European-Finnish (FIN)

AF:

0.0954

AC:

1010

AN:

10590

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0694

AC:

4722

AN:

68004

Other (OTH)

AF:

0.0669

AC:

141

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

433

867

1300

1734

2167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0664

Hom.:

148

Bravo

AF:

0.0550

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

EpiCase

AF:

0.0667

EpiControl

AF:

0.0693

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

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

Autosomal dominant cerebellar ataxia (1)

Charcot-Marie-Tooth disease (1)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

3.1

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