5-13810193-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_001369.3(DNAH5):​c.7475C>T​(p.Ala2492Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,549,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DNAH5
NM_001369.3 missense

Scores

1
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 2.41
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 Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08589715).
BP6
Variant 5-13810193-G-A is Benign according to our data. Variant chr5-13810193-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 407234.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH5NM_001369.3 linkuse as main transcriptc.7475C>T p.Ala2492Val missense_variant 45/79 ENST00000265104.5 NP_001360.1 Q8TE73

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH5ENST00000265104.5 linkuse as main transcriptc.7475C>T p.Ala2492Val missense_variant 45/791 NM_001369.3 ENSP00000265104.4 Q8TE73
DNAH5ENST00000681290.1 linkuse as main transcriptc.7430C>T p.Ala2477Val missense_variant 45/79 ENSP00000505288.1 A0A7P0Z455
DNAH5ENST00000512443.1 linkuse as main transcriptn.331C>T non_coding_transcript_exon_variant 1/33

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000619
AC:
9
AN:
145426
Hom.:
0
AF XY:
0.0000382
AC XY:
3
AN XY:
78550
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000204
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000941
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000198
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000193
AC:
27
AN:
1397216
Hom.:
0
Cov.:
34
AF XY:
0.0000203
AC XY:
14
AN XY:
689138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000634
Gnomad4 AMR exome
AF:
0.000253
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000249
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152308
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000467
AC:
4

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, no assertion criteria providedclinical testingNatera, Inc.Oct 28, 2019- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 11, 2023- -
Primary ciliary dyskinesia 3 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesAug 30, 2023The DNAH5 c.7475C>T; p.Ala2492Val variant (rs529080443), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 407234). This variant is found in the general population with an overall allele frequency of 0.0057% (10/176,774 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.06). Due to limited information, the clinical significance of this variant is uncertain at this time. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.050
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.94
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
2.5
N
REVEL
Benign
0.060
Sift
Benign
0.20
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.38
Loss of disorder (P = 0.1405);
MVP
0.27
MPC
0.093
ClinPred
0.065
T
GERP RS
4.3
Varity_R
0.021
gMVP
0.17

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: rs529080443; hg19: chr5-13810302; COSMIC: COSV99455587; API