rs202182939
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4BP6_ModerateBP7
The NM_015512.5(DNAH1):c.10582C>T(p.Leu3528=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,614,072 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 Benign (★).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.80
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.18).
BP6
?
Variant 3-52393441-C-T is Benign according to our data. Variant chr3-52393441-C-T is described in ClinVar as [Benign]. Clinvar id is 544672.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.8 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.10582C>T | p.Leu3528= | synonymous_variant | 66/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.10651C>T | p.Leu3551= | synonymous_variant | 68/80 | ||
DNAH1 | XM_017006130.2 | c.10582C>T | p.Leu3528= | synonymous_variant | 67/79 | ||
DNAH1 | XM_017006131.2 | c.10525C>T | p.Leu3509= | synonymous_variant | 67/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.10582C>T | p.Leu3528= | synonymous_variant | 66/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.11039C>T | non_coding_transcript_exon_variant | 65/77 | 2 | ||||
DNAH1 | ENST00000488988.5 | n.2368C>T | non_coding_transcript_exon_variant | 13/25 | 2 | ||||
DNAH1 | ENST00000490713.5 | c.1282C>T | p.Leu428= | synonymous_variant, NMD_transcript_variant | 9/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152250Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000433 AC: 108AN: 249248Hom.: 0 AF XY: 0.000422 AC XY: 57AN XY: 135228
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GnomAD4 exome AF: 0.000211 AC: 309AN: 1461704Hom.: 1 Cov.: 32 AF XY: 0.000221 AC XY: 161AN XY: 727136
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GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152368Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74510
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at