rs200324983

Variant names:

• chr19-55159889-C-A
• rs200324983
• NM_001256715.2:c.1163+10G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55159889-C-A
• chr19-55159889-C-G
• chr19-55159889-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BS1 BS2

The NM_001256715.2(DNAAF3):​c.1163+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,613,046 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (15 hom.)
• Consequence: DNAAF3 NM_001256715.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.554
• Publications: 0 publications found

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ENSG00000267110 (HGNC:):

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 19-55159889-C-A is Benign according to our data. Variant chr19-55159889-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00228 (347/152220) while in subpopulation NFE AF = 0.00391 (266/67998). AF 95% confidence interval is 0.00353. There are 4 homozygotes in GnomAd4. There are 159 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256715.2. 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
	DNAAF3	NM_001256715.2	MANE Select	c.1163+10G>T		intron	N/A	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.1364+10G>T		intron	N/A	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.1304+10G>T		intron	N/A	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.1163+10G>T		intron	N/A	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.1001+10G>T		intron	N/A	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*951+10G>T		intron	N/A	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152102 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00233 AC: 581 AN: 249240 AF XY: 0.00242

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000882

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00350 AC: 5112 AN: 1460826 Hom.: 15 Cov.: 33 AF XY: 0.00351 AC XY: 2552 AN XY: 726810

African (AFR) AF: 0.000598 AC: 20 AN: 33452

American (AMR) AF: 0.00103 AC: 46 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00213 AC: 184 AN: 86220

European-Finnish (FIN) AF: 0.00101 AC: 54 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00419 AC: 4656 AN: 1111314

Other (OTH) AF: 0.00252 AC: 152 AN: 60354

GnomAD4 genome AF: 0.00228 AC: 347 AN: 152220 Hom.: 4 Cov.: 31 AF XY: 0.00214 AC XY: 159 AN XY: 74424

African (AFR) AF: 0.000506 AC: 21 AN: 41532

American (AMR) AF: 0.00268 AC: 41 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00391 AC: 266 AN: 67998

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00152 Hom.: 0

Bravo AF: 0.00253

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAAF3-related disorder (1)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		-0.55
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.73		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.73		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200324983; hg19: chr19-55671257;