NM_016169.4(SUFU):c.649_661del (p.Gln217fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 2019
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:: RCV000797237.6

Allele description [Variation Report for NM_016169.4(SUFU):c.649_661del (p.Gln217fs)]

NM_016169.4(SUFU):c.649_661del (p.Gln217fs)

Gene:

SUFU:SUFU negative regulator of hedgehog signaling [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q24.32

Genomic location:

Preferred name:

NM_016169.4(SUFU):c.649_661del (p.Gln217fs)

HGVS:

NC_000010.11:g.102593687_102593699del
NG_021338.1:g.94726_94738del
NM_001178133.2:c.649_661del
NM_016169.4:c.649_661delMANE SELECT
NP_001171604.1:p.Gln217fs
NP_057253.2:p.Gln217fs
NP_057253.2:p.Gln217fs
LRG_521t1:c.649_661del
LRG_521:g.94726_94738del
LRG_521p1:p.Gln217fs
NC_000010.10:g.104353442_104353454del
NC_000010.10:g.104353444_104353456del
NM_016169.3:c.649_661del
NM_016169.3:c.649_661delCAGGGCATCCTGG

Protein change:

Q217fs

Links:

dbSNP: rs1590062899

NCBI 1000 Genomes Browser:

rs1590062899

Molecular consequence:

NM_001178133.2:c.649_661del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_016169.4:c.649_661del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Gorlin syndrome
Synonyms:: Basal cell nevus syndrome
Identifiers:: MONDO: MONDO:0007187; MedGen: C0004779; Orphanet: 377; OMIM: PS109400

Name:: Medulloblastoma (MDB)
Synonyms:: Medulloblastoma, somatic; MEDULLOBLASTOMA PREDISPOSITION SYNDROME
Identifiers:: MONDO: MONDO:0007959; MeSH: D008527; MedGen: C0025149; Orphanet: 616; OMIM: 155255; Human Phenotype Ontology: HP:0002885

Recent activity

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hypothetical protein [Flavobacterium phage FCV-1]
hypothetical protein [Flavobacterium phage FCV-1]
gi|1209836678|gb|ASD52428.1|

Protein
Chain A, Protein FRG1
Chain A, Protein FRG1
gi|183448195|pdb|2YUG|A

Protein
Homo sapiens isolate H#4 intercellular adhesion molecule 2 (ICAM2) mRNA, complet...
Homo sapiens isolate H#4 intercellular adhesion molecule 2 (ICAM2) mRNA, complete cds
gi|33340695|gb|AF340052.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000936786	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22508808, 25403219, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000936786

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2019)

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

High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age.

Brugières L, Remenieras A, Pierron G, Varlet P, Forget S, Byrde V, Bombled J, Puget S, Caron O, Dufour C, Delattre O, Bressac-de Paillerets B, Grill J.

J Clin Oncol. 2012 Jun 10;30(17):2087-93. doi: 10.1200/JCO.2011.38.7258. Epub 2012 Apr 16.

PubMed [citation]

PMID:: 22508808

Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations.

Smith MJ, Beetz C, Williams SG, Bhaskar SS, O'Sullivan J, Anderson B, Daly SB, Urquhart JE, Bholah Z, Oudit D, Cheesman E, Kelsey A, McCabe MG, Newman WG, Evans DG.

J Clin Oncol. 2014 Dec 20;32(36):4155-61. doi: 10.1200/JCO.2014.58.2569. Epub 2014 Nov 17.

PubMed [citation]

PMID:: 25403219

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000936786.6

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SUFU are known to be pathogenic (PMID: 22508808, 25403219). This variant has not been reported in the literature in individuals with SUFU-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln217Serfs*14) in the SUFU gene. It is expected to result in an absent or disrupted protein product.

#	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: Sep 16, 2024

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