rs759056367
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_001277115.2(DNAH11):āc.12100C>Gā(p.Pro4034Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 31)
Exomes š: 0.000038 ( 0 hom. )
Consequence
DNAH11
NM_001277115.2 missense
NM_001277115.2 missense
Scores
5
2
6
Clinical Significance
Conservation
PhyloP100: 4.97
Genes affected
DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.841
BP6
?
Variant 7-21873406-C-G is Benign according to our data. Variant chr7-21873406-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 575284.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.12100C>G | p.Pro4034Ala | missense_variant | 74/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.12100C>G | p.Pro4034Ala | missense_variant | 74/82 | 5 | NM_001277115.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152112Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249070Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135102
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GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727130
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152112Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74302
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2024 | The p.P4034A variant (also known as c.12100C>G), located in coding exon 74 of the DNAH11 gene, results from a C to G substitution at nucleotide position 12100. The proline at codon 4034 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at