GeneBe

rs775730815

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_015512.5(DNAH1):​c.11495delG​(p.Arg3832LeufsTer64) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAH1
NM_015512.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Publications

0 publications found
Variant links:
Genes affected
DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]
DNAH1 Gene-Disease associations (from GenCC):
  • spermatogenic failure 18
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
  • ciliary dyskinesia, primary, 37
    Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
  • primary ciliary dyskinesia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • non-syndromic male infertility due to sperm motility disorder
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH1NM_015512.5 linkc.11495delG p.Arg3832LeufsTer64 frameshift_variant Exon 72 of 78 ENST00000420323.7 NP_056327.4
DNAH1XM_017006129.2 linkc.11564delG p.Arg3855LeufsTer64 frameshift_variant Exon 74 of 80 XP_016861618.1
DNAH1XM_017006130.2 linkc.11495delG p.Arg3832LeufsTer64 frameshift_variant Exon 73 of 79 XP_016861619.1
DNAH1XM_017006131.2 linkc.11438delG p.Arg3813LeufsTer64 frameshift_variant Exon 73 of 79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkc.11495delG p.Arg3832LeufsTer64 frameshift_variant Exon 72 of 78 1 NM_015512.5 ENSP00000401514.2
DNAH1ENST00000486752.5 linkn.11952delG non_coding_transcript_exon_variant Exon 71 of 77 2
DNAH1ENST00000488988.5 linkn.3281delG non_coding_transcript_exon_variant Exon 19 of 25 2
DNAH1ENST00000490713.5 linkn.2195delG non_coding_transcript_exon_variant Exon 15 of 20 5 ENSP00000419071.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461510
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727018
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53228
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111856
Other (OTH)
AF:
0.00
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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
PhyloP100
3.6
Mutation Taster
=23/177
disease causing (fs/PTC)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs775730815; hg19: chr3-52430697; API