rs112360385
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001369.3(DNAH5):c.6715C>T(p.Pro2239Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000224 in 1,614,046 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
DNAH5
NM_001369.3 missense
NM_001369.3 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 4.70
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.019318521).
BP6
?
Variant 5-13820472-G-A is Benign according to our data. Variant chr5-13820472-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.6715C>T | p.Pro2239Ser | missense_variant | 41/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.6715C>T | p.Pro2239Ser | missense_variant | 41/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.6670C>T | p.Pro2224Ser | missense_variant | 41/79 | A1 | |||
DNAH5 | ENST00000683090.1 | n.1646C>T | non_coding_transcript_exon_variant | 6/7 |
Frequencies
GnomAD3 genomes ? AF: 0.00120 AC: 182AN: 152142Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000239 AC: 60AN: 251376Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135860
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GnomAD4 exome AF: 0.000121 AC: 177AN: 1461786Hom.: 1 Cov.: 32 AF XY: 0.000113 AC XY: 82AN XY: 727200
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GnomAD4 genome ? AF: 0.00121 AC: 184AN: 152260Hom.: 2 Cov.: 32 AF XY: 0.00111 AC XY: 83AN XY: 74442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
DNAH5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 13, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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