GeneBe

rs73055857

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001369.3(DNAH5):​c.3656G>C​(p.Arg1219Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1219C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DNAH5
NM_001369.3 missense

Scores

2
6
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.727

Publications

5 publications found
Variant links:
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]
DNAH5 Gene-Disease associations (from GenCC):
  • primary ciliary dyskinesia 3
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
  • primary ciliary dyskinesia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.769

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DNAH5
NM_001369.3
MANE Select
c.3656G>Cp.Arg1219Pro
missense
Exon 24 of 79NP_001360.1
DNAH5-AS1
NR_199035.1
n.117+10390C>G
intron
N/A

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DNAH5
ENST00000265104.5
TSL:1 MANE Select
c.3656G>Cp.Arg1219Pro
missense
Exon 24 of 79ENSP00000265104.4
DNAH5
ENST00000681290.1
c.3611G>Cp.Arg1204Pro
missense
Exon 24 of 79ENSP00000505288.1
DNAH5-AS1
ENST00000503244.2
TSL:4
n.253+10390C>G
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Benign
-0.00079
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.55
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.77
D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.7
M
PhyloP100
0.73
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.24
Sift
Uncertain
0.012
D
Polyphen
0.37
B
Vest4
0.74
MutPred
0.58
Loss of MoRF binding (P = 4e-04)
MVP
0.46
MPC
0.31
ClinPred
0.66
D
GERP RS
4.1
Varity_R
0.61
gMVP
0.84
Mutation Taster
=72/28
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs73055857; hg19: chr5-13871054; API