rs72658822
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001277115.2(DNAH11):c.12508-12T>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 0.0183 in 1,596,596 control chromosomes in the GnomAD database, including 457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 115 hom., cov: 32)
Exomes 𝑓: 0.017 ( 342 hom. )
Consequence
DNAH11
NM_001277115.2 splice_polypyrimidine_tract, intron
NM_001277115.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0002397
2
Clinical Significance
Conservation
PhyloP100: 0.300
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=-0.73).
BP6
?
Variant 7-21892413-T-C is Benign according to our data. Variant chr7-21892413-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 178736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21892413-T-C is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.12508-12T>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.12508-12T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001277115.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0308 AC: 4687AN: 152112Hom.: 114 Cov.: 32
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GnomAD3 exomes AF: 0.0217 AC: 5235AN: 241500Hom.: 89 AF XY: 0.0219 AC XY: 2871AN XY: 131034
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GnomAD4 exome AF: 0.0170 AC: 24495AN: 1444366Hom.: 342 Cov.: 30 AF XY: 0.0176 AC XY: 12625AN XY: 715580
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GnomAD4 genome ? AF: 0.0309 AC: 4697AN: 152230Hom.: 115 Cov.: 32 AF XY: 0.0310 AC XY: 2310AN XY: 74420
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | 12508-12T>C in intron 76 of DNAH11: This variant is not expected to have clinica l significance because it has been identified in 5.7% (220/3868) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs72658822). - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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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