NM_000551.4(VHL):c.123_137del (p.38SGPEE[1]) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 9, 2022
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:: RCV000222096.5

Allele description [Variation Report for NM_000551.4(VHL):c.123_137del (p.38SGPEE[1])]

NM_000551.4(VHL):c.123_137del (p.38SGPEE[1])

Gene:

VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.123_137del (p.38SGPEE[1])

HGVS:

NC_000003.11:g.10183640_10183654del
NC_000003.12:g.10141970_10141984del
NG_008212.3:g.5336_5350del
NM_000551.4:c.123_137delMANE SELECT
NM_001354723.2:c.123_137del
NM_198156.3:c.123_137del
NP_000542.1:p.38SGPEE[1]
NP_001341652.1:p.38SGPEE[1]
NP_937799.1:p.38SGPEE[1]
LRG_322:g.5336_5350del
NC_000003.11:g.10183640_10183654del
NC_000003.11:g.10183640_10183654delGAGTCCGGCCCGGAA
NC_000003.11:g.10183654_10183668del
NM_000551.3:c.123_137delAGAGTCCGGCCCGGA

Links:

dbSNP: rs863224839

NCBI 1000 Genomes Browser:

rs863224839

Molecular consequence:

NM_000551.4:c.123_137del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354723.2:c.123_137del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_198156.3:c.123_137del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000276096	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Dec 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000276096

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Dec 9, 2022)

germline

clinical testing

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

Citation Link

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

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

Gallou C, Chauveau D, Richard S, Joly D, Giraud S, Olschwang S, Martin N, Saquet C, Chrétien Y, Méjean A, Correas JM, Benoît G, Colombeau P, Grünfeld JP, Junien C, Béroud C.

Hum Mutat. 2004 Sep;24(3):215-24. Erratum in: Hum Mutat. 2004 Nov;24(5):435-6.

PubMed [citation]

PMID:: 15300849

Details of each submission

From Ambry Genetics, SCV000276096.9

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

Description

The c.123_137del15 variant (also known as p.E43_P47del) is located in coding exon 1 of the VHL gene. This variant results from an in-frame AGAGTCCGGCCCGGA deletion at nucleotide positions 123 to 137. This results in the in-frame deletion of codons 43 through 47. This alteration has been previously identified in an individual from the French VHL Registry (Gallou C, et al. Hum. Mutat. 2004 Sep;24(3):215-24). However, there is an alternate in-frame methionine 54 amino acids from the primary initiation site in VHL which is reported to result in a biologically active isoform known as VHL19 (Iliopoulos O et al. Proc. Natl. Acad. Sci. U.S.A. 1998 Sep; 95(20):11661-6. Schoenfeld A et al. Proc. Natl. Acad. Sci. U.S.A. 1998 Jul; 95(15):8817-22). The amino acids impacted by the c.123_137del15 alteration are located 5' of this alternative initiation codon and as such their significance is unclear. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Mar 5, 2024

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