7-21735655-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001277115.2(DNAH11):c.7456A>G(p.Thr2486Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,594,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T2486T) has been classified as Likely benign.
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.7456A>G | p.Thr2486Ala | missense_variant | 46/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.7456A>G | p.Thr2486Ala | missense_variant | 46/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000605912.1 | c.16A>G | p.Thr6Ala | missense_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000138 AC: 3AN: 217128Hom.: 0 AF XY: 0.0000257 AC XY: 3AN XY: 116844
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1442002Hom.: 0 Cov.: 31 AF XY: 0.00000419 AC XY: 3AN XY: 715212
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2017 | This sequence change replaces threonine with alanine at codon 2486 of the DNAH11 protein (p.Thr2486Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNAH11-related disease. This variant is present in population databases (rs752787517, ExAC 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at