NM_018139.3:c.1185G>C

Variant names:

• chr14-49633965-C-G
• rs2985686
• NM_018139.3:c.1185G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018139.3(DNAAF2):​c.1185G>C​(p.Ala395Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,527,492 control chromosomes in the GnomAD database, including 415,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39476 hom., cov: 33)
  • Exomes 𝑓: 0.73 (376412 hom.)
• Consequence: DNAAF2 NM_018139.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.81
• Publications: 20 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 14-49633965-C-G is Benign according to our data. Variant chr14-49633965-C-G is described in ClinVar as Benign. ClinVar VariationId is 95891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	NM_018139.3	MANE Select	c.1185G>C	p.Ala395Ala	synonymous	Exon 1 of 3	NP_060609.2	Q9NVR5-1
	DNAAF2	NM_001083908.2		c.1185G>C	p.Ala395Ala	synonymous	Exon 1 of 2	NP_001077377.1	Q9NVR5-2
	DNAAF2	NM_001378453.1		c.-687G>C		5_prime_UTR	Exon 1 of 2	NP_001365382.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.1185G>C	p.Ala395Ala	synonymous	Exon 1 of 3	ENSP00000298292.8	Q9NVR5-1
	DNAAF2	ENST00000406043.3	TSL:1	c.1185G>C	p.Ala395Ala	synonymous	Exon 1 of 2	ENSP00000384862.3	Q9NVR5-2

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107811 AN: 151974 Hom.: 39446 Cov.: 33

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.691

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: 0.710

GnomAD2 exomes AF: 0.644 AC: 79450 AN: 123412 AF XY: 0.641

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.728

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.764

Gnomad OTH exome AF: 0.691

GnomAD4 exome AF: 0.730 AC: 1004113 AN: 1375408 Hom.: 376412 Cov.: 83 AF XY: 0.725 AC XY: 491876 AN XY: 678326

African (AFR) AF: 0.681 AC: 21152 AN: 31054

American (AMR) AF: 0.637 AC: 22132 AN: 34720

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 18139 AN: 24652

East Asian (EAS) AF: 0.118 AC: 4157 AN: 35306

South Asian (SAS) AF: 0.548 AC: 42977 AN: 78382

European-Finnish (FIN) AF: 0.772 AC: 26076 AN: 33758

Middle Eastern (MID) AF: 0.678 AC: 2940 AN: 4338

European-Non Finnish (NFE) AF: 0.768 AC: 826629 AN: 1075798

Other (OTH) AF: 0.695 AC: 39911 AN: 57400

GnomAD4 genome AF: 0.709 AC: 107891 AN: 152084 Hom.: 39476 Cov.: 33 AF XY: 0.705 AC XY: 52424 AN XY: 74358

African (AFR) AF: 0.692 AC: 28721 AN: 41486

American (AMR) AF: 0.691 AC: 10581 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2527 AN: 3472

East Asian (EAS) AF: 0.147 AC: 755 AN: 5146

South Asian (SAS) AF: 0.533 AC: 2569 AN: 4824

European-Finnish (FIN) AF: 0.795 AC: 8427 AN: 10594

Middle Eastern (MID) AF: 0.738 AC: 214 AN: 290

European-Non Finnish (NFE) AF: 0.763 AC: 51845 AN: 67940

Other (OTH) AF: 0.709 AC: 1497 AN: 2112

Alfa AF: 0.695 Hom.: 4655

Bravo AF: 0.700

Asia WGS AF: 0.405 AC: 1403 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	3	Primary ciliary dyskinesia 10 (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.50
DANN	Benign	0.61
PhyloP100		-1.8
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: rs2985686; hg19: chr14-50100683; COSMIC: COSV53567384; COSMIC: COSV53567384;