rs148990251

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_178452.6(DNAAF1):c.1350G>A(p.Pro450Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,611,788 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

DNAAF1
NM_178452.6 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -1.57

Publications

1 publications found

Variant links:

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 13
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-84170178-G-A is Benign according to our data. Variant chr16-84170178-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 242157.

BP7

Synonymous conserved (PhyloP=-1.58 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000165 (241/1460106) while in subpopulation MID AF = 0.000697 (4/5736). AF 95% confidence interval is 0.000371. There are 0 homozygotes in GnomAdExome4. There are 125 alleles in the male GnomAdExome4 subpopulation. Median coverage is 94. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.1350G>A	p.Pro450Pro	synonymous_variant	Exon 8 of 12	ENST00000378553.10	NP_848547.4	Q8NEP3-1A0A140VJN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 link	c.1350G>A	p.Pro450Pro	synonymous_variant	Exon 8 of 12	1	NM_178452.6	ENSP00000367815.5		Q8NEP3-1

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000112

AC:

AN:

250870

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.000496

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000165

AC:

241

AN:

1460106

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

726404

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33444

American (AMR)

AF:

0.000158

AC:

AN:

44412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000697

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000167

AC:

185

AN:

1110852

Other (OTH)

AF:

0.000332

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000244

AC:

AN:

151682

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.000484

AC:

AN:

41282

American (AMR)

AF:

0.000328

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67882

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000204

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 13

Uncertain:1Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Feb 16, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:2

May 05, 2015

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.4

(source)

DANN

Benign

0.44

PhyloP100

-1.6

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