NM_002834.5(PTPN11):c.171_173del (p.Gln57_Asn58delinsHis) AND RASopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 13, 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:: RCV003041131.3

Allele description [Variation Report for NM_002834.5(PTPN11):c.171_173del (p.Gln57_Asn58delinsHis)]

NM_002834.5(PTPN11):c.171_173del (p.Gln57_Asn58delinsHis)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NM_002834.5(PTPN11):c.171_173del (p.Gln57_Asn58delinsHis)

HGVS:

NC_000012.12:g.112450351_112450353del
NG_007459.1:g.36620_36622del
NM_001330437.2:c.171_173del
NM_001374625.1:c.168_170del
NM_002834.5:c.171_173delMANE SELECT
NM_080601.3:c.171_173del
NP_001317366.1:p.Gln57_Asn58delinsHis
NP_001361554.1:p.Gln56_Asn57delinsHis
NP_002825.3:p.Gln57_Asn58delinsHis
NP_002825.3:p.Gln57_Asn58delinsHis
NP_542168.1:p.Gln57_Asn58delinsHis
LRG_614t1:c.171_173del
LRG_614:g.36620_36622del
LRG_614p1:p.Gln57_Asn58delinsHis
NC_000012.11:g.112888154_112888156del
NC_000012.11:g.112888155_112888157del
NM_002834.3:c.171_173delGAA

Molecular consequence:

NM_001330437.2:c.171_173del - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001374625.1:c.168_170del - inframe_indel - [Sequence Ontology: SO:0001820]
NM_002834.5:c.171_173del - inframe_indel - [Sequence Ontology: SO:0001820]
NM_080601.3:c.171_173del - inframe_indel - [Sequence Ontology: SO:0001820]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003354002	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003354002

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 13, 2022)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003354002.2

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

Description

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with clinical features of Noonan syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This variant, c.171_173del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the PTPN11 protein (p.Gln57_Asn58delinsHis).

#	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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