17-44901080-C-A

Variant names:

• chr17-44901080-C-A
• rs144226204
• NM_213607.3:c.82C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_213607.3(DNAAF19):​c.82C>A​(p.Arg28Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAAF19 NM_213607.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=0.648 with no splicing effect.

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.82C>A	p.Arg28Arg	synonymous	Exon 2 of 4	NP_998772.1	Q8IW40-1
	DNAAF19	NM_001258395.2		c.82C>A	p.Arg28Arg	synonymous	Exon 2 of 4	NP_001245324.1	Q8IW40-1
	DNAAF19	NM_001258396.2		c.82C>A	p.Arg28Arg	synonymous	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.82C>A	p.Arg28Arg	synonymous	Exon 2 of 4	ENSP00000391692.2	Q8IW40-1
	DNAAF19	ENST00000410006.6	TSL:2	c.82C>A	p.Arg28Arg	synonymous	Exon 2 of 4	ENSP00000387252.1	Q8IW40-1
	DNAAF19	ENST00000357776.6	TSL:2	c.82C>A	p.Arg28Arg	synonymous	Exon 2 of 4	ENSP00000350420.2	F8W6J8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451868 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722536

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32702

American (AMR) AF: 0.00 AC: 0 AN: 41042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.00 AC: 0 AN: 84368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109578

Other (OTH) AF: 0.00 AC: 0 AN: 59978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		0.65

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: rs144226204; hg19: chr17-42978448;