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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LOC127885636 [Homo sapiens]
LOC127885636 [Homo sapiens]
Gene ID:127885636

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003285827	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 23339108, 32753734, 33755199, 29068549, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003285827

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

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

#	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: Nov 10, 2024

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