rs551275210
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001277115.2(DNAH11):c.13429G>A(p.Glu4477Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.13429G>A | p.Glu4477Lys | missense_variant | Exon 82 of 82 | ENST00000409508.8 | NP_001264044.1 | |
CDCA7L | NM_018719.5 | c.*1190C>T | 3_prime_UTR_variant | Exon 10 of 10 | ENST00000406877.8 | NP_061189.2 | ||
CDCA7L | NM_001127370.3 | c.*1190C>T | 3_prime_UTR_variant | Exon 11 of 11 | NP_001120842.1 | |||
CDCA7L | NM_001127371.3 | c.*1190C>T | 3_prime_UTR_variant | Exon 9 of 9 | NP_001120843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.13429G>A | p.Glu4477Lys | missense_variant | Exon 82 of 82 | 5 | NM_001277115.2 | ENSP00000475939.1 | ||
CDCA7L | ENST00000406877 | c.*1190C>T | 3_prime_UTR_variant | Exon 10 of 10 | 1 | NM_018719.5 | ENSP00000383986.3 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151902Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248632Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134968
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461216Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 726890
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152020Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74316
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 4477 of the DNAH11 protein (p.Glu4477Lys). This variant is present in population databases (rs551275210, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of DNAH11-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 658258). 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. -
The c.13429G>A (p.E4477K) alteration is located in exon 82 (coding exon 82) of the DNAH11 gene. This alteration results from a G to A substitution at nucleotide position 13429, causing the glutamic acid (E) at amino acid position 4477 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at