NM_018699.4(PRDM5):c.974del (p.Cys325fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 5, 2023
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:: RCV001090890.32

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001246652	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2018)	germline	clinical testing	Citation Link,
SCV003525528	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26395458, 21664999, 33739556, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001246652

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Feb 1, 2018)

germline

clinical testing

Citation Link,

SCV003525528

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A role for repressive complexes and H3K9 di-methylation in PRDM5-associated brittle cornea syndrome.

Porter LF, Galli GG, Williamson S, Selley J, Knight D, Elcioglu N, Aydin A, Elcioglu M, Venselaar H, Lund AH, Bonshek R, Black GC, Manson FD.

Hum Mol Genet. 2015 Dec 1;24(23):6565-79. doi: 10.1093/hmg/ddv345. Epub 2015 Sep 22.

PubMed [citation]

PMID:: 26395458
PMCID:: PMC4634368

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

See all PubMed Citations (4)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001246652.32

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

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525528.3

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

Description

This sequence change creates a premature translational stop signal (p.Cys325Leufs*2) in the PRDM5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRDM5 are known to be pathogenic (PMID: 21664999, 26395458). This variant is present in population databases (rs766853150, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with brittle cornea syndrome (PMID: 21664999, 33739556). ClinVar contains an entry for this variant (Variation ID: 31114). 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: Jul 13, 2025

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