XM_017006129.2:c.-1812C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_017006129.2(DNAH1):​c.-1812C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,094 control chromosomes in the GnomAD database, including 10,996 homozygotes. 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: 𝑓 0.36 ( 10996 hom., cov: 32)

Consequence

DNAH1
XM_017006129.2 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

14 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: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH1XM_017006129.2 linkc.-1812C>A 5_prime_UTR_variant Exon 1 of 80 XP_016861618.1
DNAH1XM_017006130.2 linkc.-1812C>A 5_prime_UTR_variant Exon 1 of 79 XP_016861619.1 Q9P2D7-4A0A140VJI6
DNAH1XM_017006131.2 linkc.-1812C>A 5_prime_UTR_variant Exon 1 of 79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt

Frequencies

GnomAD3 genomes
AF:
0.358
AC:
54349
AN:
151976
Hom.:
10990
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.185
Gnomad AMI
AF:
0.346
Gnomad AMR
AF:
0.450
Gnomad ASJ
AF:
0.382
Gnomad EAS
AF:
0.585
Gnomad SAS
AF:
0.528
Gnomad FIN
AF:
0.483
Gnomad MID
AF:
0.358
Gnomad NFE
AF:
0.392
Gnomad OTH
AF:
0.370
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.357
AC:
54368
AN:
152094
Hom.:
10996
Cov.:
32
AF XY:
0.369
AC XY:
27409
AN XY:
74328
show subpopulations
African (AFR)
AF:
0.185
AC:
7665
AN:
41506
American (AMR)
AF:
0.451
AC:
6886
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.382
AC:
1325
AN:
3470
East Asian (EAS)
AF:
0.585
AC:
3023
AN:
5170
South Asian (SAS)
AF:
0.528
AC:
2548
AN:
4826
European-Finnish (FIN)
AF:
0.483
AC:
5098
AN:
10562
Middle Eastern (MID)
AF:
0.354
AC:
104
AN:
294
European-Non Finnish (NFE)
AF:
0.392
AC:
26620
AN:
67962
Other (OTH)
AF:
0.371
AC:
783
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
1660
3320
4981
6641
8301
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
530
1060
1590
2120
2650
<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:
0.382
Hom.:
22823
Bravo
AF:
0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.14
DANN
Benign
0.41
PhyloP100
-1.8

Splicing

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

Publications

Other links and lift over

dbSNP: rs730050; hg19: chr3-52348364; API