17-44902821-G-A

Variant names:

• chr17-44902821-G-A
• rs8079308
• NM_213607.3:c.*4G>A

Variant summary

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

The NM_213607.3(DNAAF19):​c.*4G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,533,062 control chromosomes in the GnomAD database, including 56,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5267 hom., cov: 31)
  • Exomes 𝑓: 0.27 (51592 hom.)
• Consequence: DNAAF19 NM_213607.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.198
• Publications: 14 publications found

Genes affected

DNAAF19 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF19 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 17

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• 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=-0.82).
• BP6: Variant 17-44902821-G-A is Benign according to our data. Variant chr17-44902821-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF19	NM_213607.3	c.*4G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000417826.3	NP_998772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC103	ENST00000417826.3	c.*4G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_213607.3	ENSP00000391692.2
CCDC103	ENST00000410006.6	c.*4G>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000387252.1
CCDC103	ENST00000357776.6	c.*21G>A		downstream_gene_variant		2		ENSP00000350420.2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39674 AN: 151720 Hom.: 5262 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.264

GnomAD2 exomes AF: 0.271 AC: 40562 AN: 149542 AF XY: 0.271

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.273 AC: 376894 AN: 1381224 Hom.: 51592 Cov.: 36 AF XY: 0.273 AC XY: 185576 AN XY: 678538

African (AFR) AF: 0.234 AC: 7297 AN: 31178

American (AMR) AF: 0.226 AC: 7713 AN: 34072

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 5744 AN: 24212

East Asian (EAS) AF: 0.215 AC: 7655 AN: 35552

South Asian (SAS) AF: 0.283 AC: 22296 AN: 78678

European-Finnish (FIN) AF: 0.315 AC: 15060 AN: 47800

Middle Eastern (MID) AF: 0.268 AC: 1352 AN: 5050

European-Non Finnish (NFE) AF: 0.276 AC: 294811 AN: 1067708

Other (OTH) AF: 0.263 AC: 14966 AN: 56974

GnomAD4 genome AF: 0.261 AC: 39701 AN: 151838 Hom.: 5267 Cov.: 31 AF XY: 0.261 AC XY: 19365 AN XY: 74176

African (AFR) AF: 0.233 AC: 9646 AN: 41432

American (AMR) AF: 0.227 AC: 3459 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1299 AN: 5156

South Asian (SAS) AF: 0.272 AC: 1301 AN: 4782

European-Finnish (FIN) AF: 0.316 AC: 3326 AN: 10532

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19005 AN: 67890

Other (OTH) AF: 0.262 AC: 552 AN: 2106

Alfa AF: 0.249 Hom.: 2558

Bravo AF: 0.253

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Primary ciliary dyskinesia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Primary ciliary dyskinesia 17 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		0.20
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: rs8079308; hg19: chr17-42980189; COSMIC: COSV53654651; COSMIC: COSV53654651;