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NM_001377.3(DYNC2H1):c.1360+2del AND Jeune thoracic dystrophy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 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:
RCV002516822.10

Allele description [Variation Report for NM_001377.3(DYNC2H1):c.1360+2del]

NM_001377.3(DYNC2H1):c.1360+2del

Gene:
DYNC2H1:dynein cytoplasmic 2 heavy chain 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_001377.3(DYNC2H1):c.1360+2del
HGVS:
  • NC_000011.10:g.103121038del
  • NG_016423.2:g.16608del
  • NM_001080463.2:c.1360+2del
  • NM_001377.3:c.1360+2delMANE SELECT
  • NC_000011.9:g.102991767del
  • NM_001080463.1:c.1360+2del
  • NM_001080463.1:c.1360+2delT
Links:
dbSNP: rs780539887
NCBI 1000 Genomes Browser:
rs780539887
Molecular consequence:
  • NM_001080463.2:c.1360+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001377.3:c.1360+2del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Jeune thoracic dystrophy (ATD1)
Synonyms:
Jeune syndrome; Infantile thoracic dystrophy; Thoracic pelvic phalangeal dystrophy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018770; MedGen: C0265275; OMIM: PS208500

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003285827Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 22, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families.

Baujat G, Huber C, El Hokayem J, Caumes R, Do Ngoc Thanh C, David A, Delezoide AL, Dieux-Coeslier A, Estournet B, Francannet C, Kayirangwa H, Lacaille F, Le Bourgeois M, Martinovic J, Salomon R, Sigaudy S, Malan V, Munnich A, Le Merrer M, Le Quan Sang KH, Cormier-Daire V.

J Med Genet. 2013 Feb;50(2):91-8. doi: 10.1136/jmedgenet-2012-101282.

PubMed [citation]
PMID:
23339108
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003285827.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change affects a splice site in intron 9 of the DYNC2H1 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 DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734, 33755199). This variant is present in population databases (rs780539887, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with short-rib polydactyly syndrome (PMID: 29068549). 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: 199053). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024