NM_001277115.2(DNAH11):c.13421_13453del (p.Gln4474_Lys4484del) AND Primary ciliary dyskinesia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 28, 2023
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:: RCV001216307.9

Allele description [Variation Report for NM_001277115.2(DNAH11):c.13421_13453del (p.Gln4474_Lys4484del)]

NM_001277115.2(DNAH11):c.13421_13453del (p.Gln4474_Lys4484del)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

7p15.3

Genomic location:

Preferred name:

NM_001277115.2(DNAH11):c.13421_13453del (p.Gln4474_Lys4484del)

HGVS:

NC_000007.14:g.21901124_21901156del
NG_012886.2:g.362910_362942del
NM_001127370.3:c.*1174_*1206del
NM_001127371.3:c.*1174_*1206del
NM_001277115.2:c.13421_13453delMANE SELECT
NM_018719.5:c.*1174_*1206delMANE SELECT
NP_001264044.1:p.Gln4474_Lys4484del
NC_000007.13:g.21940734_21940766del
NC_000007.13:g.21940742_21940774del
NM_001277115.1:c.13421_13453del

Links:

dbSNP: rs771508476

NCBI 1000 Genomes Browser:

rs771508476

Molecular consequence:

NM_001127370.3:c.*1174_*1206del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001127371.3:c.*1174_*1206del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_018719.5:c.*1174_*1206del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001277115.2:c.13421_13453del - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV001388097	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31772028, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001388097

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 28, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia.

Blanchon S, Legendre M, Bottier M, Tamalet A, Montantin G, Collot N, Faucon C, Dastot F, Copin B, Clement A, Filoche M, Coste A, Amselem S, Escudier E, Papon JF, Louis B.

J Med Genet. 2020 Apr;57(4):237-244. doi: 10.1136/jmedgenet-2019-106424. Epub 2019 Nov 26.

PubMed [citation]

PMID:: 31772028

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, SCV001388097.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.13421_13453del, results in the deletion of 11 amino acid(s) of the DNAH11 protein (p.Gln4474_Lys4484del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs771508476, gnomAD 0.01%). This variant has been observed in individual(s) with clinical features of primary ciliary dyskinesia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 945626). This variant disrupts a region of the DNAH11 protein in which other variant(s) (p.Pro4479Thr) have been observed in individuals with DNAH11-related conditions (PMID: 31772028). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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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