NM_213607.3:c.277-63C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_213607.3(DNAAF19):c.277-63C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,600,552 control chromosomes in the GnomAD database, including 59,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5277 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54313 hom. )

Consequence

DNAAF19
NM_213607.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.50

Publications

9 publications found

Variant links:

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, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-44902302-C-A is Benign according to our data. Variant chr17-44902302-C-A is described in ClinVar as Benign. ClinVar VariationId is 402498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF19	NM_213607.3 link	c.277-63C>A		intron_variant	Intron 3 of 3	ENST00000417826.3	NP_998772.1	Q8IW40-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC103	ENST00000417826.3 link	c.277-63C>A	intron_variant	Intron 3 of 3	1	NM_213607.3	ENSP00000391692.2	Q8IW40-1
CCDC103	ENST00000410006.6 link	c.277-63C>A	intron_variant	Intron 3 of 3	2		ENSP00000387252.1	Q8IW40-1
CCDC103	ENST00000357776.6 link	c.277-63C>A	intron_variant	Intron 3 of 3	2		ENSP00000350420.2	F8W6J8
CCDC103	ENST00000410027.5 link	c.277-16C>A	intron_variant	Intron 3 of 3	4		ENSP00000386640.1	Q8IW40-2

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39732

AN:

151988

Hom.:

5272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.264

GnomAD2 exomes

AF:

0.268

AC:

66716

AN:

248638

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.273

AC:

395513

AN:

1448446

Hom.:

54313

Cov.:

AF XY:

0.274

AC XY:

197545

AN XY:

721464

show subpopulations

African (AFR)

AF:

0.233

AC:

7734

AN:

33226

American (AMR)

AF:

0.225

AC:

10062

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6210

AN:

26072

East Asian (EAS)

AF:

0.218

AC:

8633

AN:

39624

South Asian (SAS)

AF:

0.283

AC:

24339

AN:

85986

European-Finnish (FIN)

AF:

0.316

AC:

16852

AN:

53356

Middle Eastern (MID)

AF:

0.269

AC:

1547

AN:

5742

European-Non Finnish (NFE)

AF:

0.277

AC:

304330

AN:

1099820

Other (OTH)

AF:

0.264

AC:

15806

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

16055

32111

48166

64222

80277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10046

20092

30138

40184

50230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.261

AC:

39759

AN:

152106

Hom.:

5277

Cov.:

AF XY:

0.261

AC XY:

19405

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.232

AC:

9622

AN:

41486

American (AMR)

AF:

0.226

AC:

3461

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

836

AN:

3472

East Asian (EAS)

AF:

0.252

AC:

1302

AN:

5172

South Asian (SAS)

AF:

0.272

AC:

1314

AN:

4824

European-Finnish (FIN)

AF:

0.318

AC:

3362

AN:

10580

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19029

AN:

67960

Other (OTH)

AF:

0.262

AC:

554

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1527

3055

4582

6110

7637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

1109

Bravo

AF:

0.253

Asia WGS

AF:

0.228

AC:

791

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.066

(source)

DANN

Benign

0.28

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over