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GeneBe

rs199959119

chr5-13886165-T-Achr5-13886165-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001369.3(DNAH5):c.2578-36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000727 in 1,530,352 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 0.00087 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00071 ( 3 hom. )

Consequence

DNAH5
NM_001369.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-13886165-T-A is Benign according to our data. Variant chr5-13886165-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 258013.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000711 (985/1384790) while in subpopulation MID AF= 0.0107 (55/5160). AF 95% confidence interval is 0.00841. There are 3 homozygotes in gnomad4_exome. There are 515 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH5NM_001369.3 linkuse as main transcriptc.2578-36A>T intron_variant ENST00000265104.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH5ENST00000265104.5 linkuse as main transcriptc.2578-36A>T intron_variant 1 NM_001369.3 P4
ENST00000503244.2 linkuse as main transcriptn.254-10424T>A intron_variant, non_coding_transcript_variant 4
DNAH5ENST00000681290.1 linkuse as main transcriptc.2533-36A>T intron_variant A1
ENST00000637153.1 linkuse as main transcriptn.214-10424T>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000879
AC:
128
AN:
145546
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000177
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.000873
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000642
Gnomad FIN
AF:
0.000244
Gnomad MID
AF:
0.0164
Gnomad NFE
AF:
0.00117
Gnomad OTH
AF:
0.00297
GnomAD3 exomes
AF:
0.000875
AC:
157
AN:
179332
Hom.:
0
AF XY:
0.000925
AC XY:
90
AN XY:
97286
show subpopulations
Gnomad AFR exome
AF:
0.000170
Gnomad AMR exome
AF:
0.000922
Gnomad ASJ exome
AF:
0.000792
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000236
Gnomad FIN exome
AF:
0.000457
Gnomad NFE exome
AF:
0.00135
Gnomad OTH exome
AF:
0.00165
GnomAD4 exome
AF:
0.000711
AC:
985
AN:
1384790
Hom.:
3
Cov.:
29
AF XY:
0.000749
AC XY:
515
AN XY:
687884
show subpopulations
Gnomad4 AFR exome
AF:
0.000288
Gnomad4 AMR exome
AF:
0.000680
Gnomad4 ASJ exome
AF:
0.000793
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000493
Gnomad4 FIN exome
AF:
0.000202
Gnomad4 NFE exome
AF:
0.000715
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000872
AC:
127
AN:
145562
Hom.:
0
Cov.:
32
AF XY:
0.000880
AC XY:
62
AN XY:
70482
show subpopulations
Gnomad4 AFR
AF:
0.000176
Gnomad4 AMR
AF:
0.00164
Gnomad4 ASJ
AF:
0.000873
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000646
Gnomad4 FIN
AF:
0.000244
Gnomad4 NFE
AF:
0.00117
Gnomad4 OTH
AF:
0.00296
Alfa
AF:
0.00116
Hom.:
0
Bravo
AF:
0.000910

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
1.8
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs199959119; hg19: chr5-13886274; API