rs1326134394

Variant names:

• chr17-44901050-G-A
• rs1326134394
• NM_213607.3:c.52G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-44901050-G-A
• chr17-44901050-G-C
• chr17-44901050-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_213607.3(DNAAF19):​c.52G>A​(p.Ala18Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000352 in 1,448,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: DNAAF19 NM_213607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2006228).

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.52G>A	p.Ala18Thr	missense	Exon 2 of 4	NP_998772.1	Q8IW40-1
	DNAAF19	NM_001258395.2		c.52G>A	p.Ala18Thr	missense	Exon 2 of 4	NP_001245324.1	Q8IW40-1
	DNAAF19	NM_001258396.2		c.52G>A	p.Ala18Thr	missense	Exon 2 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.52G>A	p.Ala18Thr	missense	Exon 2 of 4	ENSP00000391692.2	Q8IW40-1
	DNAAF19	ENST00000410006.6	TSL:2	c.52G>A	p.Ala18Thr	missense	Exon 2 of 4	ENSP00000387252.1	Q8IW40-1
	DNAAF19	ENST00000357776.6	TSL:2	c.52G>A	p.Ala18Thr	missense	Exon 2 of 4	ENSP00000350420.2	F8W6J8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000847 AC: 2 AN: 236178 AF XY: 0.0000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000352 AC: 51 AN: 1448542 Hom.: 0 Cov.: 31 AF XY: 0.0000347 AC XY: 25 AN XY: 720794

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.00 AC: 0 AN: 39840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39290

South Asian (SAS) AF: 0.00 AC: 0 AN: 83502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000442 AC: 49 AN: 1108880

Other (OTH) AF: 0.00 AC: 0 AN: 59846

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.098	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.28
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.96	D
Vest4		0.33
MutPred		0.17		Loss of ubiquitination at K14 (P = 0.1296)
MVP		0.78
MPC		0.58
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.069
gMVP		0.15
Mutation Taster		=91/9	polymorphism

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: rs1326134394; hg19: chr17-42978418;