14-49625359-C-CA

Position:

• chr14-49625359-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018139.3(DNAAF2):​c.*182_*183insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 321,960 control chromosomes in the GnomAD database, including 84 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (84 hom., cov: 32)
  • Exomes 𝑓: 0.053 (0 hom.)
• Consequence: DNAAF2 NM_018139.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter 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 -10 ACMG points.

• BP6: Variant 14-49625359-C-CA is Benign according to our data. Variant chr14-49625359-C-CA is described in ClinVar as [Benign]. Clinvar id is 1282890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF2	NM_018139.3	c.*182_*183insT		3_prime_UTR_variant	3/3	ENST00000298292.13
DNAAF2	NM_001083908.2	c.*182_*183insT		3_prime_UTR_variant	2/2
DNAAF2	NM_001378453.1	c.*182_*183insT		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF2	ENST00000298292.13	c.*182_*183insT		3_prime_UTR_variant	3/3	1	NM_018139.3	P2
DNAAF2	ENST00000406043.3	c.*182_*183insT		3_prime_UTR_variant	2/2	1		A2

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 2826 AN: 133798 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00470

Gnomad EAS AF: 0.00297

Gnomad SAS AF: 0.00118

Gnomad FIN AF: 0.00532

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00558

Gnomad OTH AF: 0.0178

GnomAD4 exome AF: 0.0529 AC: 9949 AN: 188134 Hom.: 0 Cov.: 0 AF XY: 0.0522 AC XY: 5026 AN XY: 96352

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.0461

Gnomad4 ASJ exome AF: 0.0467

Gnomad4 EAS exome AF: 0.0484

Gnomad4 SAS exome AF: 0.0415

Gnomad4 FIN exome AF: 0.0529

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.0562

GnomAD4 genome AF: 0.0212 AC: 2836 AN: 133826 Hom.: 84 Cov.: 32 AF XY: 0.0206 AC XY: 1327 AN XY: 64358

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00470

Gnomad4 EAS AF: 0.00298

Gnomad4 SAS AF: 0.000952

Gnomad4 FIN AF: 0.00532

Gnomad4 NFE AF: 0.00558

Gnomad4 OTH AF: 0.0177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 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;