rs201554395

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017802.4(DNAAF5):​c.1024+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000563 in 1,226,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

DNAAF5
NM_017802.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0220
Variant links:
Genes affected
DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 7-741476-G-A is Benign according to our data. Variant chr7-741476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2914443.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAAF5NM_017802.4 linkuse as main transcriptc.1024+11G>A intron_variant ENST00000297440.11
DNAAF5XM_024446813.2 linkuse as main transcriptc.1024+11G>A intron_variant
DNAAF5NR_075098.2 linkuse as main transcriptn.984+11G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAAF5ENST00000297440.11 linkuse as main transcriptc.1024+11G>A intron_variant 1 NM_017802.4 P1Q86Y56-1
DNAAF5ENST00000437419.5 linkuse as main transcriptc.341+11G>A intron_variant 5
DNAAF5ENST00000440747.5 linkuse as main transcriptc.428+11G>A intron_variant 2
DNAAF5ENST00000438961.1 linkuse as main transcriptn.493+11G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0000646
AC:
9
AN:
139238
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000516
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:
0.000109
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000627
AC:
11
AN:
175406
Hom.:
0
AF XY:
0.0000432
AC XY:
4
AN XY:
92690
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000358
Gnomad SAS exome
AF:
0.0000422
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000693
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000552
AC:
60
AN:
1087424
Hom.:
0
Cov.:
20
AF XY:
0.0000576
AC XY:
31
AN XY:
537850
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000336
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000352
Gnomad4 SAS exome
AF:
0.0000397
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000578
Gnomad4 OTH exome
AF:
0.0000248
GnomAD4 genome
AF:
0.0000646
AC:
9
AN:
139238
Hom.:
0
Cov.:
32
AF XY:
0.0000297
AC XY:
2
AN XY:
67322
show subpopulations
Gnomad4 AFR
AF:
0.0000516
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:
0.000109
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000216
Hom.:
0
Bravo
AF:
0.0000567

ClinVar

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

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeOct 27, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.9
DANN
Benign
0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs201554395; hg19: chr7-781113; API