rs2072220
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_001277115.2(DNAH11):c.7570T>A(p.Leu2524Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,878 control chromosomes in the GnomAD database, including 2 homozygotes. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2524F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.7570T>A | p.Leu2524Met | missense_variant | 46/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.7570T>A | p.Leu2524Met | missense_variant | 46/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000605912.1 | c.130T>A | p.Leu44Met | missense_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000128 AC: 32AN: 249190Hom.: 1 AF XY: 0.000192 AC XY: 26AN XY: 135182
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461678Hom.: 2 Cov.: 33 AF XY: 0.0000798 AC XY: 58AN XY: 727120
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74414
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at