rs150362958

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001256715.2(DNAAF3):c.6C>T(p.Thr2Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,794 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 13 hom., cov: 32)

Exomes 𝑓: 0.012 ( 118 hom. )

Consequence

DNAAF3
NM_001256715.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.661

Variant links:

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]

DNAAF3 links:

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

DNAAF3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-55166408-G-A is Benign according to our data. Variant chr19-55166408-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 238684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55166408-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.661 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00817 (1244/152248) while in subpopulation NFE AF= 0.0145 (985/68020). AF 95% confidence interval is 0.0137. There are 13 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 link	c.6C>T	p.Thr2Thr	synonymous_variant	Exon 2 of 12	ENST00000524407.7	NP_001243644.1	Q8N9W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 link	c.6C>T	p.Thr2Thr	synonymous_variant	Exon 2 of 12	1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1

Frequencies

GnomAD3 genomes

AF:

0.00818

AC:

1244

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00789

AC:

1959

AN:

248134

Hom.:

AF XY:

0.00786

AC XY:

1059

AN XY:

134756

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00386

Gnomad FIN exome

AF:

0.00748

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.00893

GnomAD4 exome

AF:

0.0122

AC:

17818

AN:

1461546

Hom.:

118

Cov.:

AF XY:

0.0120

AC XY:

8733

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00406

Gnomad4 FIN exome

AF:

0.00839

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.00881

GnomAD4 genome

AF:

0.00817

AC:

1244

AN:

152248

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

561

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.0145

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00784

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0110

EpiControl

AF:

0.0119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 28, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAAF3: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 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 -

Primary ciliary dyskinesia

Benign:2

Mar 18, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 2

Benign:1

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: 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

-0.43

CADD

Benign

DANN

Benign

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over