rs113024778
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001206927.2(DNAH8):āc.11340A>Gā(p.Leu3780=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,611,290 control chromosomes in the GnomAD database, including 4 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 0.0029 ( 2 hom., cov: 32)
Exomes š: 0.00027 ( 2 hom. )
Consequence
DNAH8
NM_001206927.2 synonymous
NM_001206927.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.35
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=-0.53).
BP6
?
Variant 6-38931876-A-G is Benign according to our data. Variant chr6-38931876-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 414405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.36 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00295 (449/152242) while in subpopulation AFR AF= 0.0104 (430/41532). AF 95% confidence interval is 0.00955. There are 2 homozygotes in gnomad4. There are 203 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.11340A>G | p.Leu3780= | synonymous_variant | 76/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.160+4417T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.11340A>G | p.Leu3780= | synonymous_variant | 76/93 | 5 | NM_001206927.2 | P2 | |
DNAH8-AS1 | ENST00000416948.1 | n.152+4417T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00294 AC: 448AN: 152124Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000810 AC: 201AN: 248284Hom.: 3 AF XY: 0.000559 AC XY: 75AN XY: 134258
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GnomAD4 exome AF: 0.000273 AC: 398AN: 1459048Hom.: 2 Cov.: 29 AF XY: 0.000225 AC XY: 163AN XY: 725832
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GnomAD4 genome ? AF: 0.00295 AC: 449AN: 152242Hom.: 2 Cov.: 32 AF XY: 0.00273 AC XY: 203AN XY: 74448
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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
DNAH8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 27, 2020 | 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). - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
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