NM_002834.5(PTPN11):c.276T>A (p.Asn92Lys) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 28, 2021
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:: RCV002048672.6

Allele description [Variation Report for NM_002834.5(PTPN11):c.276T>A (p.Asn92Lys)]

NM_002834.5(PTPN11):c.276T>A (p.Asn92Lys)

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.276T>A (p.Asn92Lys)

HGVS:

NC_000012.12:g.112450456T>A
NG_007459.1:g.36725T>A
NM_001330437.2:c.276T>A
NM_001374625.1:c.273T>A
NM_002834.5:c.276T>AMANE SELECT
NM_080601.3:c.276T>A
NP_001317366.1:p.Asn92Lys
NP_001361554.1:p.Asn91Lys
NP_002825.3:p.Asn92Lys
NP_542168.1:p.Asn92Lys
LRG_614:g.36725T>A
NC_000012.11:g.112888260T>A

Protein change:

N91K

Links:

dbSNP: rs2135862739

NCBI 1000 Genomes Browser:

rs2135862739

Molecular consequence:

NM_001330437.2:c.276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.273T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.276T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Homo sapiens sulfotransferase family, cytosolic, 1C, member 4, mRNA (cDNA clone ...
Homo sapiens sulfotransferase family, cytosolic, 1C, member 4, mRNA (cDNA clone MGC:149521 IMAGE:40115974), complete cds
gi|115527985|gb|BC125043.1|

Nucleotide
RecName: Full=Olfactory receptor 8H2; AltName: Full=Olfactory receptor OR11-171
RecName: Full=Olfactory receptor 8H2; AltName: Full=Olfactory receptor OR11-171
gi|38372643|sp|Q8N162.1|OR8H2_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002306758	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 28, 2021)	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

SCV002306758

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 28, 2021)

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, SCV002306758.3

#	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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PTPN11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 92 of the PTPN11 protein (p.Asn92Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine.

#	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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