chr17-44902302-C-A

Variant names:

• chr17-44902302-C-A
• rs8079610
• NM_213607.3:c.277-63C>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.277-63C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,600,552 control chromosomes in the GnomAD database, including 59,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5277 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54313 hom.)
• Consequence: DNAAF19 NM_213607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.50
• Publications: 9 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=-0.89).
• BP6: Variant 17-44902302-C-A is Benign according to our data. Variant chr17-44902302-C-A is described in ClinVar as Benign. ClinVar VariationId is 402498.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.277-63C>A		intron	N/A	NP_998772.1	Q8IW40-1
	DNAAF19	NM_001258395.2		c.277-63C>A		intron	N/A	NP_001245324.1	Q8IW40-1
	DNAAF19	NM_001258396.2		c.277-63C>A		intron	N/A	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.277-63C>A		intron	N/A	ENSP00000391692.2	Q8IW40-1
	DNAAF19	ENST00000410006.6	TSL:2	c.277-63C>A		intron	N/A	ENSP00000387252.1	Q8IW40-1
	DNAAF19	ENST00000357776.6	TSL:2	c.277-63C>A		intron	N/A	ENSP00000350420.2	F8W6J8

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39732 AN: 151988 Hom.: 5272 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.264

GnomAD2 exomes AF: 0.268 AC: 66716 AN: 248638 AF XY: 0.269

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.255

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.273 AC: 395513 AN: 1448446 Hom.: 54313 Cov.: 29 AF XY: 0.274 AC XY: 197545 AN XY: 721464

African (AFR) AF: 0.233 AC: 7734 AN: 33226

American (AMR) AF: 0.225 AC: 10062 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6210 AN: 26072

East Asian (EAS) AF: 0.218 AC: 8633 AN: 39624

South Asian (SAS) AF: 0.283 AC: 24339 AN: 85986

European-Finnish (FIN) AF: 0.316 AC: 16852 AN: 53356

Middle Eastern (MID) AF: 0.269 AC: 1547 AN: 5742

European-Non Finnish (NFE) AF: 0.277 AC: 304330 AN: 1099820

Other (OTH) AF: 0.264 AC: 15806 AN: 59948

GnomAD4 genome AF: 0.261 AC: 39759 AN: 152106 Hom.: 5277 Cov.: 32 AF XY: 0.261 AC XY: 19405 AN XY: 74358

African (AFR) AF: 0.232 AC: 9622 AN: 41486

American (AMR) AF: 0.226 AC: 3461 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1302 AN: 5172

South Asian (SAS) AF: 0.272 AC: 1314 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3362 AN: 10580

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19029 AN: 67960

Other (OTH) AF: 0.262 AC: 554 AN: 2114

Alfa AF: 0.276 Hom.: 1109

Bravo AF: 0.253

Asia WGS AF: 0.228 AC: 791 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.066
DANN	Benign	0.28
PhyloP100		-2.5
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: rs8079610; hg19: chr17-42979670; COSMIC: COSV53648926; COSMIC: COSV53648926;