rs752284064
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001277115.2(DNAH11):āc.7980A>Cā(p.Gln2660His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.7980A>C | p.Gln2660His | missense_variant | 49/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.7980A>C | p.Gln2660His | missense_variant | 49/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000605912.1 | c.474+2319A>C | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000763 AC: 19AN: 249176Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135170
GnomAD4 exome AF: 0.000226 AC: 330AN: 1461644Hom.: 0 Cov.: 31 AF XY: 0.000213 AC XY: 155AN XY: 727106
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74358
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2022 | The c.7980A>C (p.Q2660H) alteration is located in exon 49 (coding exon 49) of the DNAH11 gene. This alteration results from a A to C substitution at nucleotide position 7980, causing the glutamine (Q) at amino acid position 2660 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 2660 of the DNAH11 protein (p.Gln2660His). This variant is present in population databases (rs752284064, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DNAH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 572615). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH11 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Feb 16, 2021 | - - |
Primary ciliary dyskinesia 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at