rs60822508

Variant names:

• chr14-49633271-T-C
• rs60822508
• NM_018139.3:c.1863+16A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018139.3(DNAAF2):​c.1863+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,609,418 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (59 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (43 hom.)
• Consequence: DNAAF2 NM_018139.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.160
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• 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 14-49633271-T-C is Benign according to our data. Variant chr14-49633271-T-C is described in ClinVar as Benign. ClinVar VariationId is 261016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	NM_018139.3	MANE Select	c.1863+16A>G		intron	N/A	NP_060609.2	Q9NVR5-1
	DNAAF2	NM_001083908.2		c.1863+16A>G		intron	N/A	NP_001077377.1	Q9NVR5-2
	DNAAF2	NM_001378453.1		c.-205+212A>G		intron	N/A	NP_001365382.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.1863+16A>G		intron	N/A	ENSP00000298292.8	Q9NVR5-1
	DNAAF2	ENST00000406043.3	TSL:1	c.1863+16A>G		intron	N/A	ENSP00000384862.3	Q9NVR5-2

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2259 AN: 152220 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00388 AC: 970 AN: 249852 AF XY: 0.00270

Gnomad AFR exome AF: 0.0516

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00169 AC: 2464 AN: 1457080 Hom.: 43 Cov.: 31 AF XY: 0.00145 AC XY: 1052 AN XY: 724084

African (AFR) AF: 0.0533 AC: 1773 AN: 33238

American (AMR) AF: 0.00286 AC: 127 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00696 AC: 40 AN: 5748

European-Non Finnish (NFE) AF: 0.000235 AC: 261 AN: 1108554

Other (OTH) AF: 0.00399 AC: 240 AN: 60134

GnomAD4 genome AF: 0.0148 AC: 2262 AN: 152338 Hom.: 59 Cov.: 33 AF XY: 0.0147 AC XY: 1098 AN XY: 74500

African (AFR) AF: 0.0512 AC: 2129 AN: 41568

American (AMR) AF: 0.00510 AC: 78 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68030

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.00721 Hom.: 8

Bravo AF: 0.0168

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs60822508; hg19: chr14-50099989;