rs2985697

Positions:

• chr14-49626184-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018139.3(DNAAF2):​c.2008-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 633,026 control chromosomes in the GnomAD database, including 168,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (38226 hom., cov: 33)
  • Exomes 𝑓: 0.72 (129823 hom.)
• Consequence: DNAAF2 NM_018139.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.983

Genes affected

DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 14-49626184-T-C is Benign according to our data. Variant chr14-49626184-T-C is described in ClinVar as [Benign]. Clinvar id is 1291128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF2	NM_018139.3	c.2008-136A>G		intron_variant		ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2	c.1864-136A>G		intron_variant			NP_001077377.1
DNAAF2	NM_001378453.1	c.-204-136A>G		intron_variant			NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292.13	c.2008-136A>G		intron_variant		1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043.3	c.1864-136A>G		intron_variant		1		ENSP00000384862.3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105976 AN: 152026 Hom.: 38201 Cov.: 33

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.717 AC: 344873 AN: 480882 Hom.: 129823 AF XY: 0.717 AC XY: 171360 AN XY: 238906

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.697 AC: 106050 AN: 152144 Hom.: 38226 Cov.: 33 AF XY: 0.693 AC XY: 51543 AN XY: 74372

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.701

Alfa AF: 0.739 Hom.: 72039

Bravo AF: 0.685

Asia WGS AF: 0.402 AC: 1396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.76

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: rs2985697; hg19: chr14-50092902;