rs3809756

Variant names:

• chr17-44900676-C-A
• rs3809756
• NM_213607.3:c.-9-314C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_213607.3(DNAAF19):​c.-9-314C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,010 control chromosomes in the GnomAD database, including 34,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (34512 hom., cov: 32)
• Consequence: DNAAF19 NM_213607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72
• Publications: 4 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: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-44900676-C-A is Benign according to our data. Variant chr17-44900676-C-A is described in ClinVar as Benign. ClinVar VariationId is 1178677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 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.-9-314C>A		intron	N/A	NP_998772.1	Q8IW40-1
	DNAAF19	NM_001258395.2		c.-9-314C>A		intron	N/A	NP_001245324.1	Q8IW40-1
	DNAAF19	NM_001258396.2		c.-9-314C>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.-9-314C>A		intron	N/A	ENSP00000391692.2	Q8IW40-1
	DNAAF19	ENST00000410006.6	TSL:2	c.-9-314C>A		intron	N/A	ENSP00000387252.1	Q8IW40-1
	DNAAF19	ENST00000357776.6	TSL:2	c.-9-314C>A		intron	N/A	ENSP00000350420.2	F8W6J8

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101189 AN: 151890 Hom.: 34477 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.666 AC: 101276 AN: 152010 Hom.: 34512 Cov.: 32 AF XY: 0.659 AC XY: 48940 AN XY: 74262

African (AFR) AF: 0.811 AC: 33634 AN: 41494

American (AMR) AF: 0.568 AC: 8676 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2228 AN: 3466

East Asian (EAS) AF: 0.564 AC: 2913 AN: 5164

South Asian (SAS) AF: 0.663 AC: 3191 AN: 4812

European-Finnish (FIN) AF: 0.587 AC: 6177 AN: 10528

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42314 AN: 67962

Other (OTH) AF: 0.638 AC: 1344 AN: 2108

Alfa AF: 0.644 Hom.: 11028

Bravo AF: 0.674

Asia WGS AF: 0.603 AC: 2096 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		1.7
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: rs3809756; hg19: chr17-42978044;