14-49625359-CA-C

Position:

• chr14-49625359-CA-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_018139.3(DNAAF2):​c.*182delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 313,804 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2 hom.)
• Consequence: DNAAF2 NM_018139.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.936

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 -9 ACMG points.

• BP6: Variant 14-49625359-CA-C is Benign according to our data. Variant chr14-49625359-CA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 313273.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF2	NM_018139.3	c.*182delT		3_prime_UTR_variant	3/3	ENST00000298292.13	NP_060609.2
DNAAF2	NM_001083908.2	c.*182delT		3_prime_UTR_variant	2/2		NP_001077377.1
DNAAF2	NM_001378453.1	c.*182delT		3_prime_UTR_variant	2/2		NP_001365382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF2	ENST00000298292	c.*182delT		3_prime_UTR_variant	3/3	1	NM_018139.3	ENSP00000298292.8
DNAAF2	ENST00000406043	c.*182delT		3_prime_UTR_variant	2/2	1		ENSP00000384862.3

Frequencies

GnomAD3 genomes AF: 0.00270 AC: 361 AN: 133584 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000683

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.000942

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.00237

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.000556

GnomAD4 exome AF: 0.222 AC: 39983 AN: 180196 Hom.: 2 Cov.: 0 AF XY: 0.222 AC XY: 20464 AN XY: 92304

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.00269 AC: 359 AN: 133608 Hom.: 3 Cov.: 32 AF XY: 0.00335 AC XY: 215 AN XY: 64228

Gnomad4 AFR AF: 0.000681

Gnomad4 AMR AF: 0.00135

Gnomad4 ASJ AF: 0.000942

Gnomad4 EAS AF: 0.0198

Gnomad4 SAS AF: 0.00214

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.000554

Alfa AF: 0.000753 Hom.: 0

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs879075266; hg19: chr14-50092077;