NM_016356.4(DCDC2):c.426_557del AND Isolated neonatal sclerosing cholangitis

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 8, 2017
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000477686.13

Allele description [Variation Report for NM_016356.4(DCDC2):c.426_557del]

NM_016356.4(DCDC2):c.426_557del

Gene:

DCDC2:doublecortin domain containing 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6p22.3

Genomic location:

Preferred name:

NM_016356.4(DCDC2):c.426_557del

HGVS:

NC_000006.12:g.24301718_24301849del
NG_012829.2:g.86447_86578del
NC_000006.11:g.24301946_24302077del
NM_016356.3:c.426_557del
NM_016356.4:c.426_557del

Links:

OMIM: 605755.0006

Condition(s)

Name:: Isolated neonatal sclerosing cholangitis (NSC)
Synonyms:: Sclerosing cholangitis, neonatal
Identifiers:: MONDO: MONDO:0018816; MedGen: C4479344; OMIM: 617394

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
SCV000564218	OMIM	no assertion criteria provided	Pathogenic (May 8, 2017)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000882994	University of Washington Center for Mendelian Genomics, University of Washington	no assertion criteria provided	Pathogenic	unknown	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000564218

OMIM

no assertion criteria provided

Pathogenic
(May 8, 2017)

germline

literature only

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

SCV000882994

University of Washington Center for Mendelian Genomics, University of Washington

no assertion criteria provided

Pathogenic

unknown

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

DCDC2 Mutations Cause Neonatal Sclerosing Cholangitis.

Girard M, Bizet AA, Lachaux A, Gonzales E, Filhol E, Collardeau-Frachon S, Jeanpierre C, Henry C, Fabre M, Viremouneix L, Galmiche L, Debray D, Bole-Feysot C, Nitschke P, Pariente D, Guettier C, Lyonnet S, Heidet L, Bertholet A, Jacquemin E, Henrion-Caude A, Saunier S.

Hum Mutat. 2016 Oct;37(10):1025-9. doi: 10.1002/humu.23031. Epub 2016 Aug 24.

PubMed [citation]

PMID:: 27319779

Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.

Grammatikopoulos T, Sambrotta M, Strautnieks S, Foskett P, Knisely AS, Wagner B, Deheragoda M, Starling C, Mieli-Vergani G, Smith J; University of Washington Center for Mendelian Genomics., Bull L, Thompson RJ.

J Hepatol. 2016 Dec;65(6):1179-1187. doi: 10.1016/j.jhep.2016.07.017. Epub 2016 Jul 25.

PubMed [citation]

PMID:: 27469900
PMCID:: PMC5116266

Details of each submission

From OMIM, SCV000564218.2

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

Description

In 2 sibs, born of consanguineous parents, with neonatal sclerosing cholangitis (NSC; 617394), Girard et al. (2016) identified a homozygous 132-bp deletion (c.426_557del, NM_016356.3) in the DCDC2 gene, resulting in an in-frame deletion of 14 residues (Phe142_Arg186del) encompassing the entire exon 4 within the second doublecortin domain. The mutation, which was found by ciliary gene-targeting sequencing, segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in an in-house database of 7,477 exomes. PCR analysis of patient cells confirmed the deletion. Patient cells showed loss of DCDC2 immunostaining in the ciliary axoneme of liver cholangiocytes and fewer cilia on cholangiocytes, as well as abnormal accumulation of the mutant protein in the cytoplasm compared to controls.

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

From University of Washington Center for Mendelian Genomics, University of Washington, SCV000882994.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

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

Last Updated: Apr 20, 2024

ClinVar

Relating variation to medicine