NC_000002.11:g.(?_232952187)_(233201340_?)del AND Perlman syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 17, 2021
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:: RCV003113696.2

Allele description

NC_000002.11:g.(?_232952187)_(233201340_?)del

Gene:: DIS3L2:DIS3 like 3'-5' exoribonuclease 2 [Gene - OMIM - HGNC]
Variant type:: Deletion
Cytogenetic location:: 2q37.1
Genomic location:: Chr2: 232952187 - 233201340 (on Assembly GRCh37)
Preferred name:: NC_000002.11:g.(?_232952187)_(233201340_?)del
HGVS:: NC_000002.11:g.(?_232952187)_(233201340_?)del
This HGVS expression did not pass validation

Condition(s)

Name:: Perlman syndrome (PRLMNS)
Synonyms:: Renal hamartomas nephroblastomatosis and fetal gigantism; Nephroblastomatosis fetal ascites macrosomia and wilms tumor
Identifiers:: MONDO: MONDO:0009965; MedGen: C0796113; Orphanet: 2849; OMIM: 267000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003796775	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 17, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22306653, 23486540, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003796775

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 17, 2021)

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

Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility.

Astuti D, Morris MR, Cooper WN, Staals RH, Wake NC, Fews GA, Gill H, Gentle D, Shuib S, Ricketts CJ, Cole T, van Essen AJ, van Lingen RA, Neri G, Opitz JM, Rump P, Stolte-Dijkstra I, Müller F, Pruijn GJ, Latif F, Maher ER.

Nat Genet. 2012 Feb 5;44(3):277-84. doi: 10.1038/ng.1071.

PubMed [citation]

PMID:: 22306653

Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome.

Higashimoto K, Maeda T, Okada J, Ohtsuka Y, Sasaki K, Hirose A, Nomiyama M, Takayanagi T, Fukuzawa R, Yatsuki H, Koide K, Nishioka K, Joh K, Watanabe Y, Yoshiura K, Soejima H.

Eur J Hum Genet. 2013 Nov;21(11):1316-9. doi: 10.1038/ejhg.2013.45. Epub 2013 Mar 13.

PubMed [citation]

PMID:: 23486540
PMCID:: PMC3798850

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003796775.1

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

Description

This variant is a gross deletion of the genomic region encompassing exon(s) 6-21 of the DIS3L2 gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. This variant disrupts a region of the DIS3L2 protein in which other variant(s) (deletion of exon 9) have been determined to be pathogenic (PMID: 22306653, 23486540). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Feb 18, 2023

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