rs8079308

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-44902821-G-A
• chr17-44902821-G-C
• chr17-44902821-G-T

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, G2P, Labcorp Genetics (formerly Invitae)
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213607.3. 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
	DNAAF19	NM_213607.3	MANE Select	c.*4G>A		3_prime_UTR	Exon 4 of 4	NP_998772.1	Q8IW40-1
	DNAAF19	NM_001258395.2		c.*4G>A		3_prime_UTR	Exon 4 of 4	NP_001245324.1	Q8IW40-1
	DNAAF19	NM_001258396.2		c.*4G>A		3_prime_UTR	Exon 4 of 4	NP_001245325.1	Q8IW40-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF19	ENST00000417826.3	TSL:1 MANE Select	c.*4G>A		3_prime_UTR	Exon 4 of 4	ENSP00000391692.2	Q8IW40-1
	DNAAF19	ENST00000410006.6	TSL:2	c.*4G>A		3_prime_UTR	Exon 4 of 4	ENSP00000387252.1	Q8IW40-1
	DNAAF19	ENST00000886262.1		c.*4G>A		3_prime_UTR	Exon 4 of 4	ENSP00000556321.1

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 17 (1)

Computational scores

Source: dbNSFP v4.9

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;