NM_002834.5(PTPN11):c.642G>A (p.Gln214=) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 5, 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:: RCV000680327.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.642G>A (p.Gln214=)]

NM_002834.5(PTPN11):c.642G>A (p.Gln214=)

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.642G>A (p.Gln214=)

Other names:

p.Gln214=

HGVS:

NC_000012.12:g.112454680G>A
NG_007459.1:g.40949G>A
NM_001330437.2:c.642G>A
NM_001374625.1:c.639G>A
NM_002834.5:c.642G>AMANE SELECT
NM_080601.3:c.642G>A
NP_001317366.1:p.Gln214=
NP_001361554.1:p.Gln213=
NP_002825.3:p.Gln214=
NP_542168.1:p.Gln214=
LRG_614t1:c.642G>A
LRG_614:g.40949G>A
NC_000012.11:g.112892484G>A
NM_002834.3:c.642G>A
NM_002834.4:c.642G>A

Links:

dbSNP: rs876661383

NCBI 1000 Genomes Browser:

rs876661383

Molecular consequence:

NM_001330437.2:c.642G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374625.1:c.639G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_002834.5:c.642G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_080601.3:c.642G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000491023	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Feb 2, 2017)	germline	clinical testing	Citation Link,
SCV000858850	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Dec 27, 2017)	germline	clinical testing	Citation Link,
SCV004226383	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 5, 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

SCV000491023

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Feb 2, 2017)

germline

clinical testing

Citation Link,

SCV000858850

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Dec 27, 2017)

germline

clinical testing

Citation Link,

SCV004226383

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 5, 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	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000491023.3

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

Description

The c.642 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The c.642 G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Several in-silico splice prediction models predict that c.642 G>A may damage the natural splice donor site of intron 5 and result in abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Of note, Noonan syndrome and related rasopathies are caused by gain-of-function mutations and no loss-of-function mutations PTPN11 have been reported to date in association with a Noonan spectrum disorder. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

#	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

From Eurofins Ntd Llc (ga), SCV000858850.1

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226383.1

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

Description

PM2

#	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		1	not provided	not provided	not provided

Last Updated: May 1, 2024

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