chr7-21901013-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001277115.2(DNAH11):c.13310G>A(p.Arg4437His) variant causes a missense change. The variant allele was found at a frequency of 0.0000239 in 1,591,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4437C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.13310G>A | p.Arg4437His | missense_variant | 82/82 | ENST00000409508.8 | |
CDCA7L | NM_018719.5 | c.*1309C>T | 3_prime_UTR_variant | 10/10 | ENST00000406877.8 | ||
CDCA7L | NM_001127370.3 | c.*1309C>T | 3_prime_UTR_variant | 11/11 | |||
CDCA7L | NM_001127371.3 | c.*1309C>T | 3_prime_UTR_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.13310G>A | p.Arg4437His | missense_variant | 82/82 | 5 | NM_001277115.2 | P1 | |
CDCA7L | ENST00000406877.8 | c.*1309C>T | 3_prime_UTR_variant | 10/10 | 1 | NM_018719.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000384 AC: 9AN: 234546Hom.: 0 AF XY: 0.0000235 AC XY: 3AN XY: 127412
GnomAD4 exome AF: 0.0000222 AC: 32AN: 1438982Hom.: 0 Cov.: 33 AF XY: 0.0000252 AC XY: 18AN XY: 713562
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74348
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2016 | The p.R4437H variant (also known as c.13310G>A), located in coding exon 82 of the DNAH11 gene, results from a G to A substitution at nucleotide position 13310. The arginine at codon 4437 is replaced by histidine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5973 samples (11946 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2021 | This sequence change replaces arginine with histidine at codon 4437 of the DNAH11 protein (p.Arg4437His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs775606157, ExAC 0.005%). This variant has been observed in individual(s) with clinical features of primary ciliary dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 977532). 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. This variant disrupts the p.Arg4437 amino acid residue in DNAH11. Other variant(s) that disrupt this residue have been observed in individuals with DNAH11-related conditions (PMID: 24450482; Invitae), which suggests that this may be a clinically significant amino acid residue. 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. - |
Primary ciliary dyskinesia 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 21, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at