rs771033562
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001206927.2(DNAH8):βc.11430_11432delβ(p.Arg3812del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000561 in 1,605,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 31)
Exomes π: 0.0000055 ( 0 hom. )
Consequence
DNAH8
NM_001206927.2 inframe_deletion
NM_001206927.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.44
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_001206927.2. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.11430_11432del | p.Arg3812del | inframe_deletion | 76/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.160+4325_160+4327del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.11430_11432del | p.Arg3812del | inframe_deletion | 76/93 | 5 | NM_001206927.2 | P2 | |
DNAH8-AS1 | ENST00000416948.1 | n.152+4325_152+4327del | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000166 AC: 4AN: 240952Hom.: 0 AF XY: 0.00000767 AC XY: 1AN XY: 130296
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GnomAD4 exome AF: 0.00000551 AC: 8AN: 1453196Hom.: 0 AF XY: 0.00000415 AC XY: 3AN XY: 722566
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74304
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 11, 2022 | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 454539). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. This variant is present in population databases (rs771033562, gnomAD 0.01%). This variant, c.11430_11432del, results in the deletion of 1 amino acid(s) of the DNAH8 protein (p.Arg3812del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at