NM_018699.4(PRDM5):c.974del (p.Cys325fs) AND Brittle cornea syndrome 2

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 1, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000024110.5

Allele description [Variation Report for NM_018699.4(PRDM5):c.974del (p.Cys325fs)]

NM_018699.4(PRDM5):c.974del (p.Cys325fs)

Gene:

PRDM5:PR/SET domain 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4q27

Genomic location:

Preferred name:

NM_018699.4(PRDM5):c.974del (p.Cys325fs)

HGVS:

NC_000004.12:g.120799717del
NG_031862.2:g.128142del
NM_001300823.2:c.881del
NM_001300824.2:c.881del
NM_001379104.1:c.974del
NM_001379106.1:c.881del
NM_018699.4:c.974delMANE SELECT
NP_001287752.1:p.Cys294fs
NP_001287753.1:p.Cys294fs
NP_001366033.1:p.Cys325fs
NP_001366035.1:p.Cys294fs
NP_061169.2:p.Cys325fs
NC_000004.11:g.121720872del
NM_018699.3:c.974delG
NM_018699.4:c.974delGMANE SELECT

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

C294fs

Links:

OMIM: 614161.0005; dbSNP: rs766853150

NCBI 1000 Genomes Browser:

rs766853150

Molecular consequence:

NM_001300823.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001300824.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379104.1:c.974del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379106.1:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018699.4:c.974del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Brittle cornea syndrome 2 (BCS2)
Identifiers:: MONDO: MONDO:0013605; MedGen: C3280011; Orphanet: 90354; OMIM: 614170

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045401	OMIM	no assertion criteria provided	Pathogenic (Jun 10, 2011)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001437201	Center for Medical Genetics Ghent, University of Ghent	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 1, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 33739556
SCV001976994	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 1, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34008892, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000045401

OMIM

no assertion criteria provided

Pathogenic
(Jun 10, 2011)

germline

literature only

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

SCV001437201

Center for Medical Genetics Ghent, University of Ghent

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 1, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001976994

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 1, 2021)

unknown

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	2	1	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance.

Burkitt Wright EMM, Spencer HL, Daly SB, Manson FDC, Zeef LAH, Urquhart J, Zoppi N, Bonshek R, Tosounidis I, Mohan M, Madden C, Dodds A, Chandler KE, Banka S, Au L, Clayton-Smith J, Khan N, Biesecker LG, Wilson M, Rohrbach M, Colombi M, Giunta C, et al.

Am J Hum Genet. 2011 Jun 10;88(6):767-777. doi: 10.1016/j.ajhg.2011.05.007. Erratum in: Am J Hum Genet. 2011 Aug 12;89(2):346.

PubMed [citation]

PMID:: 21664999
PMCID:: PMC3113239

More than meets the eye: Expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome.

Dhooge T, Van Damme T, Syx D, Mosquera LM, Nampoothiri S, Radhakrishnan A, Simsek-Kiper PO, Utine GE, Bonduelle M, Migeotte I, Essawi O, Ceylaner S, Al Kindy A, Tinkle B, Symoens S, Malfait F.

Hum Mutat. 2021 Jun;42(6):711-730. doi: 10.1002/humu.24199. Epub 2021 Apr 6. Review.

PubMed [citation]

PMID:: 33739556

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000045401.1

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

Description

In a patient with brittle cornea syndrome-2 (BCS2; 614170), Burkitt Wright et al. (2011) identified homozygosity for a 1-bp deletion (974delG) in exon 9 of the PRDM5 gene, resulting in a premature termination codon. The mutation was not found in 401 control individuals.

#	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 Center for Medical Genetics Ghent, University of Ghent, SCV001437201.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (2)

#	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		2	not provided	1	not provided

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV001976994.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

PVS1, PM2, PP3, PP5

#	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: Jul 13, 2025

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