rs375668014
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001206927.2(DNAH8):āc.1952A>Gā(p.Asn651Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,608,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.1952A>G | p.Asn651Ser | missense_variant | 13/93 | ENST00000327475.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.1952A>G | p.Asn651Ser | missense_variant | 13/93 | 5 | NM_001206927.2 | P2 | |
DNAH8 | ENST00000359357.7 | c.1301A>G | p.Asn434Ser | missense_variant | 11/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.1952A>G | p.Asn651Ser | missense_variant | 12/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152252Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000227 AC: 57AN: 250576Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135698
GnomAD4 exome AF: 0.000137 AC: 200AN: 1456182Hom.: 0 Cov.: 28 AF XY: 0.000131 AC XY: 95AN XY: 724778
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 01, 2022 | The c.1952A>G (p.N651S) alteration is located in exon 13 (coding exon 12) of the DNAH8 gene. This alteration results from a A to G substitution at nucleotide position 1952, causing the asparagine (N) at amino acid position 651 to be replaced by a serine (S). 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 | Nov 06, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 651 of the DNAH8 protein (p.Asn651Ser). This variant is present in population databases (rs375668014, gnomAD 0.04%). 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: 579664). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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