rs60176657

Variant names:

• chr19-55159621-G-A
• rs60176657
• NM_001256715.2:c.1164-14C>T

Variant summary

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

The NM_001256715.2(DNAAF3):​c.1164-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,612,500 control chromosomes in the GnomAD database, including 6,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (808 hom., cov: 33)
  • Exomes 𝑓: 0.052 (6089 hom.)
• Consequence: DNAAF3 NM_001256715.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.275
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).
• BP6: Variant 19-55159621-G-A is Benign according to our data. Variant chr19-55159621-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

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.1164-14C>T		intron	N/A	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.1365-14C>T		intron	N/A	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.1305-14C>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.1164-14C>T		intron	N/A	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.1002-14C>T		intron	N/A	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*952-14C>T		intron	N/A	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10299 AN: 152146 Hom.: 797 Cov.: 33

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0775

GnomAD2 exomes AF: 0.107 AC: 26410 AN: 246984 AF XY: 0.0965

Gnomad AFR exome AF: 0.0684

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.0332

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.0272

Gnomad OTH exome AF: 0.0803

GnomAD4 exome AF: 0.0518 AC: 75646 AN: 1460236 Hom.: 6089 Cov.: 34 AF XY: 0.0525 AC XY: 38153 AN XY: 726356

African (AFR) AF: 0.0674 AC: 2254 AN: 33454

American (AMR) AF: 0.357 AC: 15871 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 914 AN: 26022

East Asian (EAS) AF: 0.242 AC: 9597 AN: 39688

South Asian (SAS) AF: 0.134 AC: 11485 AN: 85940

European-Finnish (FIN) AF: 0.0327 AC: 1743 AN: 53240

Middle Eastern (MID) AF: 0.0421 AC: 243 AN: 5768

European-Non Finnish (NFE) AF: 0.0269 AC: 29897 AN: 1111392

Other (OTH) AF: 0.0604 AC: 3642 AN: 60310

GnomAD4 genome AF: 0.0679 AC: 10332 AN: 152264 Hom.: 808 Cov.: 33 AF XY: 0.0727 AC XY: 5413 AN XY: 74454

African (AFR) AF: 0.0663 AC: 2754 AN: 41534

American (AMR) AF: 0.216 AC: 3301 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5164

South Asian (SAS) AF: 0.151 AC: 728 AN: 4830

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1813 AN: 68034

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0476 Hom.: 71

Bravo AF: 0.0829

Asia WGS AF: 0.199 AC: 690 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	Dilated Cardiomyopathy, Recessive (1)
-	-	1	Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome (1)
-	-	1	Familial restrictive cardiomyopathy (1)
-	-	1	Hypertrophic cardiomyopathy (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.6
DANN	Benign	0.90
PhyloP100		-0.28
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs60176657;

hg19: chr19-55670989;

COSMIC: COSV61275226;

COSMIC: COSV61275226;