GeneBe

NM_001080463.2:c.3181C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001080463.2(DYNC2H1):​c.3181C>T​(p.Leu1061Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

DYNC2H1
NM_001080463.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

0 publications found
Variant links:
Genes affected
DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]
DYNC2H1 Gene-Disease associations (from GenCC):
  • asphyxiating thoracic dystrophy 3
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
  • Jeune syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • short rib-polydactyly syndrome, Majewski type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • short rib-polydactyly syndrome, Verma-Naumoff type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP7
Synonymous conserved (PhyloP=1.12 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYNC2H1NM_001080463.2 linkc.3181C>T p.Leu1061Leu synonymous_variant Exon 22 of 90 ENST00000650373.2 NP_001073932.1 Q8NCM8-2
DYNC2H1NM_001377.3 linkc.3181C>T p.Leu1061Leu synonymous_variant Exon 22 of 89 ENST00000375735.7 NP_001368.2 Q8NCM8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNC2H1ENST00000650373.2 linkc.3181C>T p.Leu1061Leu synonymous_variant Exon 22 of 90 NM_001080463.2 ENSP00000497174.1 Q8NCM8-2
DYNC2H1ENST00000375735.7 linkc.3181C>T p.Leu1061Leu synonymous_variant Exon 22 of 89 1 NM_001377.3 ENSP00000364887.2 Q8NCM8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.13e-7
AC:
1
AN:
1401618
Hom.:
0
Cov.:
31
AF XY:
0.00000145
AC XY:
1
AN XY:
691464
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31906
American (AMR)
AF:
0.00
AC:
0
AN:
35946
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25162
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36392
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78464
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49656
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5686
European-Non Finnish (NFE)
AF:
9.26e-7
AC:
1
AN:
1080330
Other (OTH)
AF:
0.00
AC:
0
AN:
58076
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
7.8
DANN
Benign
0.65
PhyloP100
1.1

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

Other links and lift over

dbSNP: rs200466720; hg19: chr11-103024116; API