NM_031427.4(DNAL1):c.415C>G (p.Leu139Val) AND Primary ciliary dyskinesia 16

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 23, 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:: RCV001088090.13

Allele description [Variation Report for NM_031427.4(DNAL1):c.415C>G (p.Leu139Val)]

NM_031427.4(DNAL1):c.415C>G (p.Leu139Val)

Gene:

DNAL1:dynein axonemal light chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_031427.4(DNAL1):c.415C>G (p.Leu139Val)

HGVS:

NC_000014.9:g.73689398C>G
NG_028083.2:g.49524C>G
NM_001201366.2:c.298C>G
NM_031427.4:c.415C>GMANE SELECT
NP_001188295.1:p.Leu100Val
NP_113615.2:p.Leu139Val
NC_000014.8:g.74156101C>G
NG_028083.1:g.49524C>G
NM_001201366.1:c.298C>G
NM_031427.3:c.415C>G

Protein change:

L100V

Links:

dbSNP: rs141873943

NCBI 1000 Genomes Browser:

rs141873943

Molecular consequence:

NM_001201366.2:c.298C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_031427.4:c.415C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary ciliary dyskinesia 16
Synonyms:: CILIARY DYSKINESIA, PRIMARY, 16, WITH OR WITHOUT SITUS INVERSUS
Identifiers:: MONDO: MONDO:0013525; MedGen: C3151460; Orphanet: 244; OMIM: 614017

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000290964	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 23, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003799687	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Oct 6, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000290964

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 23, 2024)

germline

clinical testing

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

SCV003799687

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Oct 6, 2023)

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

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000290964.10

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003799687.3

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

Description

The DNAL1 c.415C>G; p.Leu139Val variant (rs141873943; ClinVar Variation ID: 178765) has been observed in a cohort of patients referred for Bronchiectasis, but no additional evidence of causality was provided (Olm 2019). This variant is found in the Latino population with an allele frequency of 0.34% (88/25652 alleles) in the Genome Aggregation Database. The leucine at codon 139 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.241). Due to limited information, the clinical significance of the p.Leu139Val variant is uncertain at this time. References: Olm MAK et al. Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil. Sci Rep. 2019 Jun 18;9(1):8693. PMID: 31213628

#	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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