rs142704524

chr16-84150359-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_178452.6(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 NM_178452.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.515

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF1	NM_178452.6	c.352+17G>C		intron_variant		ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10	c.352+17G>C		intron_variant		1	NM_178452.6	P1
DNAAF1	ENST00000567918.5	c.352+17G>C		intron_variant, NMD_transcript_variant		1
DNAAF1	ENST00000563093.5	c.352+17G>C		intron_variant, NMD_transcript_variant		2
DNAAF1	ENST00000570298.5	n.506+17G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2125 AN: 152208 Hom.: 25 Cov.: 33

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.: 26 AF XY: 0.0136 AC XY: 1845 AN XY: 135594

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.: 25 AF XY: 0.0167 AC XY: 11817 AN XY: 707422

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.: 25 Cov.: 33 AF XY: 0.0139 AC XY: 1033 AN XY: 74488

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.: 6

Bravo AF: 0.0126

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

- -

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

Other links and lift over

dbSNP: rs142704524; hg19: chr16-84183964;