Variant 16-84150359-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000378553.10(DNAAF1):c.352+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,567,880 control chromosomes in the GnomAD database, including 280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 33)

Exomes 𝑓: 0.017 ( 255 hom. )

Consequence

DNAAF1
ENST00000378553.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.515

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]

DNAAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-84150359-G-C is Benign according to our data. Variant chr16-84150359-G-C is described in ClinVar as [Benign]. Clinvar id is 262952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84150359-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0139 (2124/152326) while in subpopulation NFE AF= 0.0198 (1346/68040). AF 95% confidence interval is 0.0189. There are 25 homozygotes in gnomad4. There are 1033 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF1	NM_178452.6 linkuse as main transcript	c.352+17G>C		intron_variant		ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 linkuse as main transcript	c.352+17G>C	intron_variant	1	NM_178452.6	ENSP00000367815	P1	Q8NEP3-1
DNAAF1	ENST00000567918.5 linkuse as main transcript	c.352+17G>C	intron_variant, NMD_transcript_variant	1		ENSP00000455154
DNAAF1	ENST00000563093.5 linkuse as main transcript	c.352+17G>C	intron_variant, NMD_transcript_variant	2		ENSP00000457373		Q8NEP3-3
DNAAF1	ENST00000570298.5 linkuse as main transcript	n.506+17G>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2125

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0133

AC:

3339

AN:

250818

Hom.:

AF XY:

0.0136

AC XY:

1845

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00346

Gnomad AMR exome

AF:

0.00940

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00428

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0170

AC:

24097

AN:

1415554

Hom.:

255

Cov.:

AF XY:

0.0167

AC XY:

11817

AN XY:

707422

show subpopulations

Gnomad4 AFR exome

AF:

0.00342

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00416

Gnomad4 FIN exome

AF:

0.0241

Gnomad4 NFE exome

AF:

0.0193

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0139

AC:

2124

AN:

152326

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1033

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00330

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0198

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Primary ciliary dyskinesia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 03, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

DANN

Benign

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over