NM_002834.5(PTPN11):c.392A>G (p.Lys131Arg) AND RASopathy

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

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Aug 19, 2019
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000654924.10

Allele description

NM_002834.5(PTPN11):c.392A>G (p.Lys131Arg)

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.392A>G (p.Lys131Arg)

HGVS:

NC_000012.12:g.112453254A>G
NG_007459.1:g.39523A>G
NM_001330437.2:c.392A>G
NM_001374625.1:c.389A>G
NM_002834.5:c.392A>GMANE SELECT
NM_080601.3:c.392A>G
NP_001317366.1:p.Lys131Arg
NP_001361554.1:p.Lys130Arg
NP_002825.3:p.Lys131Arg
NP_542168.1:p.Lys131Arg
LRG_614t1:c.392A>G
LRG_614:g.39523A>G
NC_000012.11:g.112891058A>G
NM_002834.3:c.392A>G
NM_002834.4(PTPN11):c.392A>G
NM_002834.4:c.392A>G
c.392A>G

Protein change:

K130R

Links:

dbSNP: rs397516805

NCBI 1000 Genomes Browser:

rs397516805

Molecular consequence:

NM_001330437.2:c.392A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.389A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.392A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.392A>G - 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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Anomodon attenuatus CcmFc (ccmFC) gene, complete cds; mitochondrial
Anomodon attenuatus CcmFc (ccmFC) gene, complete cds; mitochondrial
gi|578361118|gb|KC663349.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000776830	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 21, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001192858	ClinGen RASopathy Variant Curation Expert Panel	reviewed by expert panel (ClinGen RASopathy ACMG Specifications v1)	Likely benign (Aug 19, 2019)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000776830

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 21, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001192858

ClinGen RASopathy Variant Curation Expert Panel

reviewed by expert panel

(ClinGen RASopathy ACMG Specifications v1)

Likely benign
(Aug 19, 2019)

germline

curation

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, curation

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 Invitae, SCV000776830.7

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

#	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 ClinGen RASopathy Variant Curation Expert Panel, SCV001192858.1

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

Description

The c.392A>G (p.Lys131Arg) variant in the PTPN11 gene has been identified in a patient with an alternate molecular basis of disease (BP5; Laboratory for Molecular Medicine internal data; VCV000013351.2, GeneDx internal data; VCV000013351.2). The filtering allele frequency of p.Lys131Arg variant is 0.042% for East Asian alleles in the gnomAD database (14/19952 with 95% CI), which is a high enough frequency to be considered strong evidence for the variant being benign by the ClinGen RASopathy Expert Panel (BS1). The variant is located in the PTPN11 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2 not met due to case level data indicative of benign). This variant was observed in a healthy adult individual who did not have clinical features of a RASopathy (BS2 not met; Universite Paris Diderot internal data). The ClinGen RASopathy Expert Panel has classified the p.Lys131Arg variant as likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BS1, BP5.

#	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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