rs116164504
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001206927.2(DNAH8):āc.384G>Cā(p.Glu128Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,606,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E128K) has been classified as Uncertain significance.
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.384G>C | p.Glu128Asp | missense_variant | 2/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.384G>C | p.Glu128Asp | missense_variant | 2/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000373278.8 | c.384G>C | p.Glu128Asp | missense_variant | 2/5 | 1 | |||
DNAH8 | ENST00000449981.6 | c.384G>C | p.Glu128Asp | missense_variant | 1/82 | 5 | |||
DNAH8 | ENST00000359357.7 | c.-183G>C | 5_prime_UTR_variant | 1/91 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000299 AC: 71AN: 237516Hom.: 0 AF XY: 0.000338 AC XY: 44AN XY: 130280
GnomAD4 exome AF: 0.000476 AC: 692AN: 1454070Hom.: 1 Cov.: 32 AF XY: 0.000475 AC XY: 343AN XY: 722862
GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74484
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2022 | The c.384G>C (p.E128D) alteration is located in exon 2 (coding exon 1) of the DNAH8 gene. This alteration results from a G to C substitution at nucleotide position 384, causing the glutamic acid (E) at amino acid position 128 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 18, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 128 of the DNAH8 protein (p.Glu128Asp). This variant is present in population databases (rs116164504, gnomAD 0.06%). 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: 407275). 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"). 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