chr14-49626184-T-C

Variant names:

• chr14-49626184-T-C
• rs2985697
• NM_018139.3:c.2008-136A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 publications found

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]

DNAAF2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 10

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	NM_018139.3	MANE Select	c.2008-136A>G		intron	N/A	NP_060609.2
	DNAAF2	NM_001083908.2		c.1864-136A>G		intron	N/A	NP_001077377.1
	DNAAF2	NM_001378453.1		c.-204-136A>G		intron	N/A	NP_001365382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.2008-136A>G		intron	N/A	ENSP00000298292.8
	DNAAF2	ENST00000406043.3	TSL:1	c.1864-136A>G		intron	N/A	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

African (AFR) AF: 0.642 AC: 7199 AN: 11210

American (AMR) AF: 0.663 AC: 6368 AN: 9606

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 7829 AN: 10626

East Asian (EAS) AF: 0.106 AC: 2531 AN: 23942

South Asian (SAS) AF: 0.539 AC: 6433 AN: 11932

European-Finnish (FIN) AF: 0.771 AC: 13932 AN: 18060

Middle Eastern (MID) AF: 0.676 AC: 1175 AN: 1738

European-Non Finnish (NFE) AF: 0.765 AC: 283016 AN: 369954

Other (OTH) AF: 0.688 AC: 16390 AN: 23814

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

African (AFR) AF: 0.649 AC: 26929 AN: 41510

American (AMR) AF: 0.687 AC: 10489 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2526 AN: 3468

East Asian (EAS) AF: 0.147 AC: 764 AN: 5182

South Asian (SAS) AF: 0.533 AC: 2568 AN: 4814

European-Finnish (FIN) AF: 0.795 AC: 8416 AN: 10580

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51905 AN: 67998

Other (OTH) AF: 0.701 AC: 1481 AN: 2114

Alfa AF: 0.728 Hom.: 120003

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

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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: rs2985697; hg19: chr14-50092902;