NM_000278.5(PAX2):c.221_226dup (p.Glu74_Thr75dup) AND Renal coloboma syndrome

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Aug 24, 2016
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:: RCV000014811.25

Allele description [Variation Report for NM_000278.5(PAX2):c.221_226dup (p.Glu74_Thr75dup)]

NM_000278.5(PAX2):c.221_226dup (p.Glu74_Thr75dup)

Gene:

PAX2:paired box 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

10q24.31

Genomic location:

Preferred name:

NM_000278.5(PAX2):c.221_226dup (p.Glu74_Thr75dup)

HGVS:

NC_000010.11:g.100750702_100750707dup
NG_008680.2:g.19994_19999dup
NM_000278.5:c.221_226dupMANE SELECT
NM_001304569.2:c.314_319dup
NM_003987.5:c.221_226dup
NM_003988.5:c.221_226dup
NM_003989.5:c.221_226dup
NM_003990.5:c.221_226dup
NP_000269.3:p.Glu74_Thr75dup
NP_001291498.1:p.Glu105_Thr106dup
NP_003978.3:p.Glu74_Thr75dup
NP_003979.2:p.Glu74_Thr75dup
NP_003980.3:p.Glu74_Thr75dup
NP_003981.3:p.Glu74_Thr75dup
NC_000010.10:g.102510456_102510457insCGAGAC
NC_000010.10:g.102510459_102510464dup
NG_008680.1:g.9992_9997dup
NM_003990.3:c.221_226dupAGACCG
NM_003990.4:c.221_226dup
NP_003981.2:p.Glu74_Thr75dup

Links:

OMIM: 167409.0007; dbSNP: rs387906530

NCBI 1000 Genomes Browser:

rs387906530

Molecular consequence:

NM_000278.5:c.221_226dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001304569.2:c.314_319dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_003987.5:c.221_226dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_003988.5:c.221_226dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_003989.5:c.221_226dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_003990.5:c.221_226dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Observations:

Condition(s)

Name:: Renal coloboma syndrome (PAPRS)
Synonyms:: RENAL-COLOBOMA SYNDROME WITH MACULAR ABNORMALITIES; Papillorenal syndrome; Optic nerve coloboma with renal disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007352; MedGen: C1852759; Orphanet: 1475; OMIM: 120330

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000035066	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2012)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9760197, 22213154
SCV000891288	Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 24, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22213154, 9760197, 25741868
SCV001593013	Precision Medicine Center, Zhengzhou University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000035066

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2012)

germline

literature only

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

SCV000891288

Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 24, 2016)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001593013

Precision Medicine Center, Zhengzhou University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

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	germline	yes	1	not provided	not provided	1	not provided	clinical testing, research

Citations

PubMed

Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database.

Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Jensen UB, Cochat P, DeCramer S, Dixon J, Drouin R, Falk MJ, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Morinière V, Mowat D, et al.

Hum Mutat. 2012 Mar;33(3):457-66. doi: 10.1002/humu.22020. Epub 2012 Jan 31.

PubMed [citation]

PMID:: 22213154

Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330).

Devriendt K, Matthijs G, Van Damme B, Van Caesbroeck D, Eccles M, Vanrenterghem Y, Fryns JP, Leys A.

Hum Genet. 1998 Aug;103(2):149-53.

PubMed [citation]

PMID:: 9760197

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000035066.1

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

Description

In a sporadic case of renal-coloboma syndrome (120330) in a male patient with an Oriental mother and Caucasian father, Devriendt et al. (1998) found that the disorder was caused by heterozygosity for a duplication of 6 nucleotides 763-768, i.e., insertion GAGACC after nucleotide 768, resulting in the duplication of amino acid residues glu74 and thr75.

Based on nucleotide numbering reflecting the cDNA transcript with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence, Bower et al. (2012) referred to the 768_769insgagacc mutation as 221_226dup, and to the predicted effect on the protein as Glu74_Thr75dup.

#	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 Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota, SCV000891288.1

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

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

From Precision Medicine Center, Zhengzhou University, SCV001593013.1

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

Description

PM1:Located in a mutational hot spot PM2:not found in gnomAD PM4:Protein length changes as a result of in-frame deletions PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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