NM_001206927.2:c.2159A>T
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_001206927.2(DNAH8):c.2159A>T(p.Asp720Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
Publications
- spermatogenic failure 46Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
- spermatogenic failure 5Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
- primary ciliary dyskinesiaInheritance: AR Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.2159A>T | p.Asp720Val | missense_variant | Exon 16 of 93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.2159A>T | p.Asp720Val | missense_variant | Exon 16 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000359357.7 | c.1508A>T | p.Asp503Val | missense_variant | Exon 14 of 91 | 2 | ENSP00000352312.3 | |||
DNAH8 | ENST00000449981.6 | c.2159A>T | p.Asp720Val | missense_variant | Exon 15 of 82 | 5 | ENSP00000415331.2 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152188Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000398 AC: 10AN: 251164 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461606Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727108 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000131 AC: 20AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74346 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2159A>T (p.D720V) alteration is located in exon 16 (coding exon 15) of the DNAH8 gene. This alteration results from a A to T substitution at nucleotide position 2159, causing the aspartic acid (D) at amino acid position 720 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Primary ciliary dyskinesia Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 720 of the DNAH8 protein (p.Asp720Val). This variant is present in population databases (rs138373981, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 525380). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at