NM_001369.3(DNAH5):c.6988+2T>C AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 22, 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:: RCV001849586.7

Allele description [Variation Report for NM_001369.3(DNAH5):c.6988+2T>C]

NM_001369.3(DNAH5):c.6988+2T>C

Gene:

DNAH5:dynein axonemal heavy chain 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p15.2

Genomic location:

Preferred name:

NM_001369.3(DNAH5):c.6988+2T>C

HGVS:

NC_000005.10:g.13817546A>G
NG_013081.2:g.131935T>C
NM_001369.3:c.6988+2T>CMANE SELECT
NC_000005.9:g.13817655A>G
NM_001369.2:c.6988+2T>C

Links:

dbSNP: rs2151806960

NCBI 1000 Genomes Browser:

rs2151806960

Molecular consequence:

NM_001369.3:c.6988+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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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Homo sapiens inositol polyphosphate-5-phosphatase J (INPP5J), transcript variant...
Homo sapiens inositol polyphosphate-5-phosphatase J (INPP5J), transcript variant 1, mRNA
gi|1519243392|ref|NM_001284285.2|

Nucleotide
Brp/Blh family beta-carotene 15,15'-monooxygenase [Caenorhabditis elegans]
Brp/Blh family beta-carotene 15,15'-monooxygenase [Caenorhabditis elegans]
gi|17567671|ref|NP_509905.1|

Protein
Nocomis effusus voucher YPM 18826 zic family member 1 (zic1) gene, partial cds
Nocomis effusus voucher YPM 18826 zic family member 1 (zic1) gene, partial cds
gi|336051608|gb|JF949859.1|

Nucleotide
Phenacobius uranops voucher UTEIC 44.12256 ectodermal-neural cortex 1-like prote...
Phenacobius uranops voucher UTEIC 44.12256 ectodermal-neural cortex 1-like protein (ENC1) gene, partial cds
gi|336051564|gb|JF949837.1|

Nucleotide
Plant sample from Triticum turgidum subsp. durum
Plant sample from Triticum turgidum subsp. durum

biosample

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002106429	Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics	no assertion criteria provided	Likely pathogenic (Aug 1, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002295265	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 22, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25802884, 30067075, 16199547, 11788826, 16627867, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002106429

Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics

no assertion criteria provided

Likely pathogenic
(Aug 1, 2018)

germline

literature only

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

SCV002295265

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 22, 2023)

germline

clinical testing

PubMed (6)
[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	yes	2	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Carrier frequencies of eleven mutations in eight genes associated with primary ciliary dyskinesia in the Ashkenazi Jewish population.

Fedick AM, Jalas C, Treff NR, Knowles MR, Zariwala MA.

Mol Genet Genomic Med. 2015 Mar;3(2):137-42. doi: 10.1002/mgg3.124. Epub 2014 Dec 6.

PubMed [citation]

PMID:: 25802884
PMCID:: PMC4367086

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.

Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW.

Am J Respir Crit Care Med. 2019 Jan 15;199(2):190-198. doi: 10.1164/rccm.201803-0548OC.

PubMed [citation]

PMID:: 30067075
PMCID:: PMC6353004

See all PubMed Citations (6)

Details of each submission

From Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics, SCV002106429.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002295265.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1344585). Disruption of this splice site has been observed in individual(s) with primary ciliary dyskinesia (PMID: 25802884, 30067075; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 42 of the DNAH5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867).

#	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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