rs2985697

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-49626184-T-A
• chr14-49626184-T-C
• chr14-49626184-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018139.3(DNAAF2):​c.2008-136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAAF2 NM_018139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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>T		intron	N/A	NP_060609.2
	DNAAF2	NM_001083908.2		c.1864-136A>T		intron	N/A	NP_001077377.1
	DNAAF2	NM_001378453.1		c.-204-136A>T		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>T		intron	N/A	ENSP00000298292.8
	DNAAF2	ENST00000406043.3	TSL:1	c.1864-136A>T		intron	N/A	ENSP00000384862.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 482200 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 239576

African (AFR) AF: 0.00 AC: 0 AN: 11234

American (AMR) AF: 0.00 AC: 0 AN: 9630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10646

East Asian (EAS) AF: 0.00 AC: 0 AN: 23980

South Asian (SAS) AF: 0.00 AC: 0 AN: 11974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 370998

Other (OTH) AF: 0.00 AC: 0 AN: 23886

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	23
DANN	Benign	0.72
PhyloP100		-0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.79		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.79		Position offset: 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;