NM_178452.6(DNAAF1):c.1712C>T (p.Pro571Leu) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 22, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001969743.6

Allele description [Variation Report for NM_178452.6(DNAAF1):c.1712C>T (p.Pro571Leu)]

NM_178452.6(DNAAF1):c.1712C>T (p.Pro571Leu)

Gene:

DNAAF1:dynein axonemal assembly factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.1

Genomic location:

Preferred name:

NM_178452.6(DNAAF1):c.1712C>T (p.Pro571Leu)

HGVS:

NC_000016.10:g.84175946C>T
NG_021174.1:g.35688C>T
NM_001318756.1:c.1004C>T
NM_178452.6:c.1712C>TMANE SELECT
NP_001305685.1:p.Pro335Leu
NP_848547.4:p.Pro571Leu
NC_000016.9:g.84209552C>T
NM_178452.4:c.1712C>T

Protein change:

P335L

Links:

dbSNP: rs199727292

NCBI 1000 Genomes Browser:

rs199727292

Molecular consequence:

NM_001318756.1:c.1004C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_178452.6:c.1712C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary ciliary dyskinesia
Synonyms:: Ciliary dyskinesia
Identifiers:: MONDO: MONDO:0016575; MedGen: C0008780; OMIM: PS244400; Human Phenotype Ontology: HP:0012265

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002221797	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002712936	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 6, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002221797

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002712936

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 6, 2015)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002221797.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with DNAAF1-related conditions. This variant is present in population databases (rs199727292, ExAC 0.006%). This sequence change replaces proline with leucine at codon 571 of the DNAAF1 protein (p.Pro571Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002712936.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.P571L variant (also known as c.1712C>T), located in coding exon 11 of the DNAAF1 gene, results from a C to T substitution at nucleotide position 1712. The proline at codon 571 is replaced by leucine, an amino acid with a few similar properties. This variant was previously reported in the SNPDatabase as rs199727292. This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.; however this position was not covered in the ESP. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine