rs200622578
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_015512.5(DNAH1):āc.11043A>Gā(p.Thr3681=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,613,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0011 ( 1 hom., cov: 32)
Exomes š: 0.000081 ( 0 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.77
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 3-52395382-A-G is Benign according to our data. Variant chr3-52395382-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 544676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.77 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00105 (160/152338) while in subpopulation AFR AF= 0.0037 (154/41584). AF 95% confidence interval is 0.00323. There are 1 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.11043A>G | p.Thr3681= | synonymous_variant | 69/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.11112A>G | p.Thr3704= | synonymous_variant | 71/80 | ||
DNAH1 | XM_017006130.2 | c.11043A>G | p.Thr3681= | synonymous_variant | 70/79 | ||
DNAH1 | XM_017006131.2 | c.10986A>G | p.Thr3662= | synonymous_variant | 70/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.11043A>G | p.Thr3681= | synonymous_variant | 69/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000999 AC: 152AN: 152220Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000209 AC: 52AN: 248886Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135062
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GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461550Hom.: 0 Cov.: 32 AF XY: 0.0000757 AC XY: 55AN XY: 727030
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GnomAD4 genome ? AF: 0.00105 AC: 160AN: 152338Hom.: 1 Cov.: 32 AF XY: 0.00102 AC XY: 76AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
DNAH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at