NM_001277115.2(DNAH11):c.7325A>G (p.Lys2442Arg) AND Primary ciliary dyskinesia

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 29, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001088819.10

Allele description [Variation Report for NM_001277115.2(DNAH11):c.7325A>G (p.Lys2442Arg)]

NM_001277115.2(DNAH11):c.7325A>G (p.Lys2442Arg)

Gene:

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.7325A>G (p.Lys2442Arg)

HGVS:

NC_000007.14:g.21725869A>G
NG_012886.2:g.187655A>G
NM_001277115.2:c.7325A>GMANE SELECT
NP_001264044.1:p.Lys2442Arg
NC_000007.13:g.21765487A>G
NM_001277115.1:c.7325A>G

Protein change:

K2442R

Links:

dbSNP: rs114286628

NCBI 1000 Genomes Browser:

rs114286628

Molecular consequence:

NM_001277115.2:c.7325A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000562002	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002669760	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Dec 15, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000562002

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 29, 2024)

germline

clinical testing

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

SCV002669760

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Dec 15, 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	1	not provided	not provided	1	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, SCV000562002.8

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

#	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, SCV002669760.1

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

Description

The p.K2442R variant (also known as c.7325A>G), located in coding exon 45 of the DNAH11 gene, results from an A to G substitution at nucleotide position 7325. The lysine at codon 2442 is replaced by arginine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs114286628. Based on data from the 1000 Genomes Project, the G allele has an overall frequency of approximately 0.14% (3/2098) total alleles studied. The highest observed frequency was 1.14% (2/176) Yoruba alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the G allele has an overall frequency of approximately 0.05% (6/11828) total alleles studied, having been observed in 0.16% (6/3654) African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by SIFT. 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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