rs72657378
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001277115.2(DNAH11):c.9337-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,612,198 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 26 hom. )
Consequence
DNAH11
NM_001277115.2 splice_polypyrimidine_tract, intron
NM_001277115.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.002776
2
Clinical Significance
Conservation
PhyloP100: 1.92
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 7-21778949-T-C is Benign according to our data. Variant chr7-21778949-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 178730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21778949-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1885/152260) while in subpopulation AFR AF= 0.0425 (1767/41534). AF 95% confidence interval is 0.0409. There are 42 homozygotes in gnomad4. There are 904 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 42 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.9337-9T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.9337-9T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001277115.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0124 AC: 1880AN: 152142Hom.: 43 Cov.: 32
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GnomAD3 exomes AF: 0.00321 AC: 796AN: 247918Hom.: 19 AF XY: 0.00232 AC XY: 312AN XY: 134474
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GnomAD4 exome AF: 0.00131 AC: 1910AN: 1459938Hom.: 26 Cov.: 31 AF XY: 0.00108 AC XY: 786AN XY: 726016
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GnomAD4 genome ? AF: 0.0124 AC: 1885AN: 152260Hom.: 42 Cov.: 32 AF XY: 0.0121 AC XY: 904AN XY: 74434
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | 9337-9T>C in intron 56 of DNAH11: This variant is not expected to have clinical significance because it has been identified in 3.7% (140/3794) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs72657378). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Primary ciliary dyskinesia 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 16, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at