chr5-13913884-G-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001369.3(DNAH5):​c.1395C>T​(p.Ser465Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,613,478 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 183 hom., cov: 33)
Exomes 𝑓: 0.0031 ( 158 hom. )

Consequence

DNAH5
NM_001369.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.16

Publications

3 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 5-13913884-G-A is Benign according to our data. Variant chr5-13913884-G-A is described in ClinVar as [Benign]. Clinvar id is 226594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH5NM_001369.3 linkc.1395C>T p.Ser465Ser synonymous_variant Exon 11 of 79 ENST00000265104.5 NP_001360.1 Q8TE73

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH5ENST00000265104.5 linkc.1395C>T p.Ser465Ser synonymous_variant Exon 11 of 79 1 NM_001369.3 ENSP00000265104.4 Q8TE73

Frequencies

GnomAD3 genomes
AF:
0.0263
AC:
4004
AN:
151956
Hom.:
182
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0910
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00944
Gnomad ASJ
AF:
0.00664
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000515
Gnomad OTH
AF:
0.0167
GnomAD2 exomes
AF:
0.00755
AC:
1895
AN:
250926
AF XY:
0.00582
show subpopulations
Gnomad AFR exome
AF:
0.0929
Gnomad AMR exome
AF:
0.00576
Gnomad ASJ exome
AF:
0.00834
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000644
Gnomad OTH exome
AF:
0.00376
GnomAD4 exome
AF:
0.00314
AC:
4587
AN:
1461404
Hom.:
158
Cov.:
34
AF XY:
0.00276
AC XY:
2008
AN XY:
727008
show subpopulations
African (AFR)
AF:
0.0970
AC:
3246
AN:
33462
American (AMR)
AF:
0.00599
AC:
268
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00723
AC:
189
AN:
26124
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39668
South Asian (SAS)
AF:
0.000394
AC:
34
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53382
Middle Eastern (MID)
AF:
0.00729
AC:
42
AN:
5764
European-Non Finnish (NFE)
AF:
0.000342
AC:
380
AN:
1111682
Other (OTH)
AF:
0.00707
AC:
427
AN:
60364
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
227
454
682
909
1136
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
112
224
336
448
560
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0264
AC:
4017
AN:
152074
Hom.:
183
Cov.:
33
AF XY:
0.0260
AC XY:
1933
AN XY:
74334
show subpopulations
African (AFR)
AF:
0.0910
AC:
3778
AN:
41498
American (AMR)
AF:
0.00943
AC:
144
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00664
AC:
23
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000515
AC:
35
AN:
67920
Other (OTH)
AF:
0.0166
AC:
35
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
184
368
552
736
920
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
40
80
120
160
200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0126
Hom.:
36
Bravo
AF:
0.0293
Asia WGS
AF:
0.00664
AC:
23
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.00119

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:3
Jan 16, 2015
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 16, 2020
Natera, Inc.
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

not specified Benign:2
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 21, 2013
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Ser465Ser in exon 11 of DNAH5: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 9.5% (418/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs34580014). -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Feb 28, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Primary ciliary dyskinesia 3 Benign:2
Mar 06, 2017
Counsyl
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
8.5
DANN
Benign
0.72
PhyloP100
1.2
Mutation Taster
=95/5
polymorphism (auto)

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: rs34580014; hg19: chr5-13913993; API