NM_006265.3(RAD21):c.877C>T (p.Gln293Ter) AND Cornelia de Lange syndrome 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 7, 2024
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:: RCV004781989.1

Allele description [Variation Report for NM_006265.3(RAD21):c.877C>T (p.Gln293Ter)]

NM_006265.3(RAD21):c.877C>T (p.Gln293Ter)

Gene:

RAD21:RAD21 cohesin complex component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.11

Genomic location:

Preferred name:

NM_006265.3(RAD21):c.877C>T (p.Gln293Ter)

HGVS:

NC_000008.11:g.116856226G>A
NG_032862.1:g.23641C>T
NM_006265.3:c.877C>TMANE SELECT
NP_006256.1:p.Gln293Ter
NP_006256.1:p.Gln293Ter
LRG_772t1:c.877C>T
LRG_772:g.23641C>T
LRG_772p1:p.Gln293Ter
NC_000008.10:g.117868465G>A
NM_006265.2:c.877C>T

Protein change:

Q293*

Molecular consequence:

NM_006265.3:c.877C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Cornelia de Lange syndrome 4 (CDLS4)
Synonyms:: CORNELIA DE LANGE SYNDROME 4 WITH OR WITHOUT MIDLINE BRAIN DEFECTS
Identifiers:: MONDO: MONDO:0013864; MedGen: C3553517; Orphanet: 199; OMIM: 614701

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005393880	Molecular Genetics Laboratory, Motol Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 7, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22633399, 32193685, 24378232, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005393880

Molecular Genetics Laboratory, Motol Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 7, 2024)

germline

clinical testing

PubMed (4)
[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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

RAD21 mutations cause a human cohesinopathy.

Deardorff MA, Wilde JJ, Albrecht M, Dickinson E, Tennstedt S, Braunholz D, Mönnich M, Yan Y, Xu W, Gil-Rodríguez MC, Clark D, Hakonarson H, Halbach S, Michelis LD, Rampuria A, Rossier E, Spranger S, Van Maldergem L, Lynch SA, Gillessen-Kaesbach G, Lüdecke HJ, Ramsay RG, et al.

Am J Hum Genet. 2012 Jun 8;90(6):1014-27. doi: 10.1016/j.ajhg.2012.04.019. Epub 2012 May 24.

PubMed [citation]

PMID:: 22633399
PMCID:: PMC3370273

Delineation of phenotypes and genotypes related to cohesin structural protein RAD21.

Krab LC, Marcos-Alcalde I, Assaf M, Balasubramanian M, Andersen JB, Bisgaard AM, Fitzpatrick DR, Gudmundsson S, Huisman SA, Kalayci T, Maas SM, Martinez F, McKee S, Menke LA, Mulder PA, Murch OD, Parker M, Pie J, Ramos FJ, Rieubland C, Rosenfeld Mokry JA, Scarano E, et al.

Hum Genet. 2020 May;139(5):575-592. doi: 10.1007/s00439-020-02138-2. Epub 2020 Mar 19.

PubMed [citation]

PMID:: 32193685
PMCID:: PMC7170815

See all PubMed Citations (4)

Details of each submission

From Molecular Genetics Laboratory, Motol Hospital, SCV005393880.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

This variant was detected in a male with abnormality of the face, tracheal stenosis, pylorostenosis, failure to thrive and suspected diagnosis of Cornelia de Lange syndrome (CDLS). The segregation molecular genetic analysis in his parents was not performed. The relevant medical/scientific publications report on pathogenic RAD21 gene variants as a molecular cause of CDLS (PMID:22633399;32193685;24378232). This novel variant correlates with the clinical manifestation of CDLS. To conclude, the variant is classified as likely pathogenic (ACMG PVS1, PM2).

#	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		1	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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