NM_002834.5(PTPN11):c.332+17T>G AND not specified

Germline classification:: Benign (2 submissions)
Last evaluated:: Jun 22, 2020
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:: RCV000157684.4

Allele description [Variation Report for NM_002834.5(PTPN11):c.332+17T>G]

NM_002834.5(PTPN11):c.332+17T>G

Gene:

PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NM_002834.5(PTPN11):c.332+17T>G

HGVS:

NC_000012.12:g.112450529T>G
NG_007459.1:g.36798T>G
NM_001330437.2:c.332+17T>G
NM_001374625.1:c.329+17T>G
NM_002834.5:c.332+17T>GMANE SELECT
NM_080601.3:c.332+17T>G
LRG_614t1:c.332+17T>G
LRG_614:g.36798T>G
NC_000012.11:g.112888333T>G
NM_002834.3:c.332+17T>G
NM_002834.4:c.332+17T>G

Links:

dbSNP: rs115658366

NCBI 1000 Genomes Browser:

rs115658366

Molecular consequence:

NM_001330437.2:c.332+17T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001374625.1:c.329+17T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_002834.5:c.332+17T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_080601.3:c.332+17T>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000207665	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	no assertion criteria provided	Benign (Jan 15, 2015)	germline	clinical testing
SCV001372262	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jun 22, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15385933, 14644997, 19047918, 17972951, 25395418, 27069254 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000207665

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

no assertion criteria provided

Benign
(Jan 15, 2015)

germline

clinical testing

SCV001372262

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Jun 22, 2020)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group.

Loh ML, Reynolds MG, Vattikuti S, Gerbing RB, Alonzo TA, Carlson E, Cheng JW, Lee CM, Lange BJ, Meshinchi S; Children's Cancer Group..

Leukemia. 2004 Nov;18(11):1831-4.

PubMed [citation]

PMID:: 15385933

Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis.

Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, Cheng JW, Lee CM, Stokoe D, Bonifas JM, Curtiss NP, Gotlib J, Meshinchi S, Le Beau MM, Emanuel PD, Shannon KM.

Blood. 2004 Mar 15;103(6):2325-31. Epub 2003 Nov 26.

PubMed [citation]

PMID:: 14644997

See all PubMed Citations (6)

Details of each submission

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV000207665.1

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

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001372262.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: PTPN11 c.332+17T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00089 in 250870 control chromosomes, predominantly at a frequency of 0.0071 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 114-fold of the estimated maximal expected allele frequency for a pathogenic variant in PTPN11 causing Noonan Syndrome And Related Conditions phenotype (6.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. A ClinVar submitter (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

#	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 29, 2024

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