GeneBe

NM_178452.6:c.-216_-215insCC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178452.6(DNAAF1):​c.-216_-215insCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 518,672 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

DNAAF1
NM_178452.6 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410

Publications

0 publications found
Variant links:
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAAF1NM_178452.6 linkc.-216_-215insCC upstream_gene_variant ENST00000378553.10 NP_848547.4 Q8NEP3-1A0A140VJN4
HSDL1NM_031463.5 linkc.-215_-214insGG upstream_gene_variant ENST00000219439.9 NP_113651.4 Q3SXM5-1I6L975

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAAF1ENST00000378553.10 linkc.-216_-215insCC upstream_gene_variant 1 NM_178452.6 ENSP00000367815.5 Q8NEP3-1
HSDL1ENST00000219439.9 linkc.-215_-214insGG upstream_gene_variant 1 NM_031463.5 ENSP00000219439.4 Q3SXM5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000193
AC:
1
AN:
518672
Hom.:
0
Cov.:
8
AF XY:
0.00000375
AC XY:
1
AN XY:
266554
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
10874
American (AMR)
AF:
0.00
AC:
0
AN:
15774
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12074
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24238
South Asian (SAS)
AF:
0.00
AC:
0
AN:
44014
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
24988
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1926
European-Non Finnish (NFE)
AF:
0.00000279
AC:
1
AN:
358180
Other (OTH)
AF:
0.00
AC:
0
AN:
26604
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.041

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1241570624; hg19: chr16-84178830; API