NM_001277115.2(DNAH11):c.13445G>A (p.Arg4482Lys) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 30, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000688478.3

Allele description [Variation Report for NM_001277115.2(DNAH11):c.13445G>A (p.Arg4482Lys)]

NM_001277115.2(DNAH11):c.13445G>A (p.Arg4482Lys)

Genes:

CDCA7L:cell division cycle associated 7 like [Gene - OMIM - HGNC]
DNAH11:dynein axonemal heavy chain 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p15.3

Genomic location:

Preferred name:

NM_001277115.2(DNAH11):c.13445G>A (p.Arg4482Lys)

HGVS:

NC_000007.14:g.21901148G>A
NG_012886.2:g.362934G>A
NM_001127370.3:c.*1174C>T
NM_001127371.3:c.*1174C>T
NM_001277115.2:c.13445G>AMANE SELECT
NM_018719.5:c.*1174C>TMANE SELECT
NP_001264044.1:p.Arg4482Lys
NC_000007.13:g.21940766G>A
NM_001277115.1:c.13445G>A

Protein change:

R4482K

Links:

dbSNP: rs191791959

NCBI 1000 Genomes Browser:

rs191791959

Molecular consequence:

NM_001127370.3:c.*1174C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001127371.3:c.*1174C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_018719.5:c.*1174C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001277115.2:c.13445G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000816091	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 30, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000816091

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 30, 2018)

germline

clinical testing

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000816091.1

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

Description

This sequence change replaces arginine with lysine at codon 4482 of the DNAH11 protein (p.Arg4482Lys). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs191791959, ExAC 0.003%). This variant has not been reported in the literature in individuals with DNAH11-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#	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: Sep 29, 2024

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