5-13820374-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001369.3(DNAH5):​c.6813C>G​(p.Cys2271Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DNAH5
NM_001369.3 missense

Scores

7
10
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.912

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH5NM_001369.3 linkc.6813C>G p.Cys2271Trp missense_variant Exon 41 of 79 ENST00000265104.5 NP_001360.1 Q8TE73

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH5ENST00000265104.5 linkc.6813C>G p.Cys2271Trp missense_variant Exon 41 of 79 1 NM_001369.3 ENSP00000265104.4 Q8TE73
DNAH5ENST00000681290.1 linkc.6768C>G p.Cys2256Trp missense_variant Exon 41 of 79 ENSP00000505288.1 A0A7P0Z455
DNAH5ENST00000683090.1 linkn.1744C>G non_coding_transcript_exon_variant Exon 6 of 7

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
148038
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1458650
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725702
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
148038
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
72392
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.73
D
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Pathogenic
3.7
H
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-8.9
D
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.69
Gain of MoRF binding (P = 0.0105);
MVP
0.76
MPC
0.51
ClinPred
0.99
D
GERP RS
1.9
Varity_R
0.96
gMVP
0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373542336; hg19: chr5-13820483; API