rs142704524

Variant names:

• chr16-84150359-G-C
• rs142704524
• NM_178452.6:c.352+17G>C

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 0.515
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 262952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.352+17G>C		intron_variant	Intron 3 of 11	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.352+17G>C		intron_variant	Intron 3 of 11	1	NM_178452.6	ENSP00000367815.5
DNAAF1	ENST00000567918.5	n.352+17G>C		intron_variant	Intron 3 of 6	1		ENSP00000455154.1
DNAAF1	ENST00000563093.5	n.352+17G>C		intron_variant	Intron 3 of 10	2		ENSP00000457373.1
DNAAF1	ENST00000570298.5	n.506+17G>C		intron_variant	Intron 3 of 10	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

GnomAD2 exomes AF: 0.0133 AC: 3339 AN: 250818 AF XY: 0.0136

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 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

African (AFR) AF: 0.00342 AC: 111 AN: 32500

American (AMR) AF: 0.0101 AC: 449 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 302 AN: 25894

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00416 AC: 355 AN: 85298

European-Finnish (FIN) AF: 0.0241 AC: 1287 AN: 53356

Middle Eastern (MID) AF: 0.00808 AC: 46 AN: 5692

European-Non Finnish (NFE) AF: 0.0193 AC: 20637 AN: 1069852

Other (OTH) AF: 0.0155 AC: 910 AN: 58848

GnomAD4 genome AF: 0.0139 AC: 2124 AN: 152326 Hom.: 25 Cov.: 33 AF XY: 0.0139 AC XY: 1033 AN XY: 74488

African (AFR) AF: 0.00330 AC: 137 AN: 41564

American (AMR) AF: 0.0145 AC: 222 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4834

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1346 AN: 68040

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 13 Benign:1

Oct 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.27
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142704524; hg19: chr16-84183964;