NM_001377.3(DYNC2H1):c.1760G>A (p.Arg587His) AND Jeune thoracic dystrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 26, 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:: RCV003587068.2

Allele description [Variation Report for NM_001377.3(DYNC2H1):c.1760G>A (p.Arg587His)]

NM_001377.3(DYNC2H1):c.1760G>A (p.Arg587His)

Gene:

DYNC2H1:dynein cytoplasmic 2 heavy chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_001377.3(DYNC2H1):c.1760G>A (p.Arg587His)

HGVS:

NC_000011.10:g.103125198G>A
NG_016423.2:g.20768G>A
NM_001080463.2:c.1760G>A
NM_001377.3:c.1760G>AMANE SELECT
NP_001073932.1:p.Arg587His
NP_001368.2:p.Arg587His
NC_000011.9:g.102995927G>A

Protein change:

R587H

Molecular consequence:

NM_001080463.2:c.1760G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377.3:c.1760G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004276399	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19361615, 23339108, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004276399

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 26, 2023)

germline

clinical testing

PubMed (3)
[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

Ciliary abnormalities due to defects in the retrograde transport protein DYNC2H1 in short-rib polydactyly syndrome.

Merrill AE, Merriman B, Farrington-Rock C, Camacho N, Sebald ET, Funari VA, Schibler MJ, Firestein MH, Cohn ZA, Priore MA, Thompson AK, Rimoin DL, Nelson SF, Cohn DH, Krakow D.

Am J Hum Genet. 2009 Apr;84(4):542-9. doi: 10.1016/j.ajhg.2009.03.015.

PubMed [citation]

PMID:: 19361615
PMCID:: PMC2667993

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004276399.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYNC2H1 protein function. This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 587 of the DYNC2H1 protein (p.Arg587His). This variant disrupts the p.Arg587 amino acid residue in DYNC2H1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19361615, 23339108). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Sep 29, 2024

ClinVar

Relating variation to medicine