rs17512439

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001376.5(DYNC1H1):​c.7137G>A​(p.Leu2379Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0016 in 1,614,210 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L2379L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0088 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 23 hom. )

Consequence

DYNC1H1
NM_001376.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 6.65

Publications

1 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 14-102015227-G-A is Benign according to our data. Variant chr14-102015227-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0088 (1341/152318) while in subpopulation AFR AF = 0.0307 (1278/41566). AF 95% confidence interval is 0.0293. There are 20 homozygotes in GnomAd4. There are 673 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 1341 AD gene.

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DYNC1H1
NM_001376.5
MANE Select
c.7137G>Ap.Leu2379Leu
synonymous
Exon 35 of 78NP_001367.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DYNC1H1
ENST00000360184.10
TSL:1 MANE Select
c.7137G>Ap.Leu2379Leu
synonymous
Exon 35 of 78ENSP00000348965.4Q14204
DYNC1H1
ENST00000681574.1
c.7137G>Ap.Leu2379Leu
synonymous
Exon 35 of 77ENSP00000505523.1A0A7P0T9C4
DYNC1H1
ENST00000679720.1
c.7137G>Ap.Leu2379Leu
synonymous
Exon 35 of 78ENSP00000505938.1A0A7P0TA13

Frequencies

GnomAD3 genomes
AF:
0.00881
AC:
1341
AN:
152200
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0308
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00431
GnomAD2 exomes
AF:
0.00242
AC:
609
AN:
251462
AF XY:
0.00170
show subpopulations
Gnomad AFR exome
AF:
0.0315
Gnomad AMR exome
AF:
0.00228
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.000651
GnomAD4 exome
AF:
0.000844
AC:
1234
AN:
1461892
Hom.:
23
Cov.:
31
AF XY:
0.000723
AC XY:
526
AN XY:
727246
show subpopulations
African (AFR)
AF:
0.0287
AC:
962
AN:
33480
American (AMR)
AF:
0.00221
AC:
99
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39700
South Asian (SAS)
AF:
0.0000696
AC:
6
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00121
AC:
7
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000531
AC:
59
AN:
1112010
Other (OTH)
AF:
0.00164
AC:
99
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
83
166
249
332
415
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
34
68
102
136
170
<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:
0.00880
AC:
1341
AN:
152318
Hom.:
20
Cov.:
32
AF XY:
0.00904
AC XY:
673
AN XY:
74478
show subpopulations
African (AFR)
AF:
0.0307
AC:
1278
AN:
41566
American (AMR)
AF:
0.00333
AC:
51
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68030
Other (OTH)
AF:
0.00426
AC:
9
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
71
143
214
286
357
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00454
Hom.:
3
Bravo
AF:
0.00991
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

ClinVar submissions
Significance:Benign/Likely benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
6
not specified (6)
-
-
3
not provided (3)
-
-
2
Charcot-Marie-Tooth disease axonal type 2O (2)
-
-
1
Autosomal dominant cerebellar ataxia (1)
-
-
1
Charcot-Marie-Tooth disease (1)
-
-
1
Charcot-Marie-Tooth disease axonal type 2O;C3281202:Intellectual disability, autosomal dominant 13;C5780022:Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures (1)
-
-
1
Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
11
DANN
Benign
0.73
PhyloP100
6.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17512439; hg19: chr14-102481564; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.