NM_017950.4(CCDC40):c.1414C>T (p.Arg472Trp) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 21, 2024
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:: RCV000816546.12

Allele description [Variation Report for NM_017950.4(CCDC40):c.1414C>T (p.Arg472Trp)]

NM_017950.4(CCDC40):c.1414C>T (p.Arg472Trp)

Gene:

CCDC40:coiled-coil domain 40 molecular ruler complex subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_017950.4(CCDC40):c.1414C>T (p.Arg472Trp)

HGVS:

NC_000017.11:g.80058954C>T
NG_029761.1:g.27323C>T
NM_001243342.2:c.1414C>T
NM_001330508.2:c.1414C>T
NM_017950.4:c.1414C>TMANE SELECT
NP_001230271.1:p.Arg472Trp
NP_001317437.1:p.Arg472Trp
NP_060420.2:p.Arg472Trp
NC_000017.10:g.78032753C>T
NM_017950.3:c.1414C>T

Protein change:

R472W

Links:

dbSNP: rs187993089

NCBI 1000 Genomes Browser:

rs187993089

Molecular consequence:

NM_001243342.2:c.1414C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330508.2:c.1414C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_017950.4:c.1414C>T - 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

Recent activity

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Cecropterus dobra voucher NVG-11182
Cecropterus dobra voucher NVG-11182

biosample
Cecropterus nevada nevada voucher LACM:NVG-14114A10
Cecropterus nevada nevada voucher LACM:NVG-14114A10

biosample
cytochrome c oxidase subunit I, partial (mitochondrion) [Ceratodictyon sp.]
cytochrome c oxidase subunit I, partial (mitochondrion) [Ceratodictyon sp.]
gi|2422684310|gb|WBN91020.1|

Protein
radial spoke head 14 homolog [Homo sapiens]
radial spoke head 14 homolog [Homo sapiens]
gi|7657530|ref|NP_055248.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000957061	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001810039	UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002699705	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 21, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000957061

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

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

SCV001810039

UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 27, 2021)

germline

clinical testing

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

SCV002699705

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 21, 2024)

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	1	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000957061.4

#	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, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 472 of the CCDC40 protein (p.Arg472Trp). This variant is present in population databases (rs187993089, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. ClinVar contains an entry for this variant (Variation ID: 659522). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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

From UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill, SCV001810039.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing (GTR000576399.1)	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	(GTR000576399.1)	1	not provided	1	not provided

From Ambry Genetics, SCV002699705.3

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

Description

The c.1414C>T (p.R472W) alteration is located in exon 9 (coding exon 9) of the CCDC40 gene. This alteration results from a C to T substitution at nucleotide position 1414, causing the arginine (R) at amino acid position 472 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration 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: Sep 29, 2024

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