rs45622336
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001206927.2(DNAH8):c.4401G>A(p.Thr1467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,612,986 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0071 ( 54 hom. )
Consequence
DNAH8
NM_001206927.2 synonymous
NM_001206927.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.69
Genes affected
DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 6-38837977-G-A is Benign according to our data. Variant chr6-38837977-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 238647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.69 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00419 (638/152228) while in subpopulation NFE AF= 0.00776 (528/68004). AF 95% confidence interval is 0.00722. There are 6 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.4401G>A | p.Thr1467= | synonymous_variant | 33/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.4401G>A | p.Thr1467= | synonymous_variant | 33/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.3750G>A | p.Thr1250= | synonymous_variant | 31/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.4401G>A | p.Thr1467= | synonymous_variant | 32/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00420 AC: 639AN: 152110Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00452 AC: 1133AN: 250666Hom.: 4 AF XY: 0.00469 AC XY: 635AN XY: 135504
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GnomAD4 exome AF: 0.00705 AC: 10305AN: 1460758Hom.: 54 Cov.: 29 AF XY: 0.00691 AC XY: 5023AN XY: 726736
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GnomAD4 genome ? AF: 0.00419 AC: 638AN: 152228Hom.: 6 Cov.: 32 AF XY: 0.00388 AC XY: 289AN XY: 74428
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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
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | DNAH8: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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