NM_001122681.2(SH3BP2):c.1253C>T (p.Pro418Leu) AND Fibrous dysplasia of jaw

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

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jan 28, 2022
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:: RCV000007983.10

Allele description

NM_001122681.2(SH3BP2):c.1253C>T (p.Pro418Leu)

Gene:

SH3BP2:SH3 domain binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_001122681.2(SH3BP2):c.1253C>T (p.Pro418Leu)

HGVS:

NC_000004.12:g.2831582C>T
NG_011609.1:g.43560C>T
NM_001122681.2:c.1253C>TMANE SELECT
NM_001145855.2:c.1337C>T
NM_001145856.2:c.1424C>T
NM_003023.4:c.1253C>T
NP_001116153.1:p.Pro418Leu
NP_001139327.1:p.Pro446Leu
NP_001139328.1:p.Pro475Leu
NP_003014.3:p.Pro418Leu
LRG_1334t1:c.1253C>T
LRG_1334t2:c.1337C>T
LRG_1334:g.43560C>T
LRG_1334p1:p.Pro418Leu
LRG_1334p2:p.Pro446Leu
NC_000004.11:g.2833309C>T
NM_001122681.1:c.1253C>T
NM_001122681.2:c.1253C>T
P78314:p.Pro418Leu

Protein change:

P418L; PRO418LEU

Links:

UniProtKB: P78314#VAR_013260; OMIM: 602104.0001; dbSNP: rs121909146

NCBI 1000 Genomes Browser:

rs121909146

Molecular consequence:

NM_001122681.2:c.1253C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145855.2:c.1337C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145856.2:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003023.4:c.1253C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fibrous dysplasia of jaw (CRBM)
Synonyms:: Cherubism
Identifiers:: MONDO: MONDO:0007315; MedGen: C0008029; Orphanet: 184; OMIM: 118400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028188	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000996316	Clinical Genetics Laboratory, Federal University of Health Sciences of Porto Alegre	no assertion criteria provided	Pathogenic (Mar 18, 2019)	maternal	research
SCV001223199	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 16, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17321449, 18596838, 28644570, 22153077, 11381256, 27272835, 23298620, 28492532
SCV002577549	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	maternal	yes	1	not provided	not provided	1	yes	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A new mutation in the SH3BP2 gene showing reduced penetrance in a family affected with cherubism.

de Lange J, van Maarle MC, van den Akker HP, Redeker EJ.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103(3):378-81. Epub 2006 Sep 26. No abstract available.

PubMed [citation]

PMID:: 17321449

Investigation of the SH3BP2 gene mutation in cherubism.

Lee JY, Jung YS, Kim SA, Lee SH, Ahn SG, Yoon JH.

Acta Med Okayama. 2008 Jun;62(3):209-12.

PubMed [citation]

PMID:: 18596838

See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000028188.1

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

Description

Ueki et al. (2001) found a pro418-to-leu (P418L) mutation of the SH3BP2 gene in patients with cherubism (118400).

#	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 Clinical Genetics Laboratory, Federal University of Health Sciences of Porto Alegre, SCV000996316.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	yes	research	not provided

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

From Invitae, SCV001223199.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant disrupts the p.Pro418 amino acid residue in SH3BP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17321449, 18596838, 28644570, 23298620, 11381256). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported to affect SH3BP2 protein function (PMID: 22153077). This variant has been observed in individuals and families affected with cherubism (PMID: 11381256, 27272835, 23298620). ClinVar contains an entry for this variant (Variation ID: 7547). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 418 of the SH3BP2 protein (p.Pro418Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV002577549.1

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

Description

PS4, PM1, PM5, PM2, PP3, PP5

#	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: Feb 14, 2024

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