NM_000245.4(MET):c.2265-49G>C AND Renal cell carcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 5, 2023
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:: RCV001868729.4

Allele description [Variation Report for NM_000245.4(MET):c.2265-49G>C]

NM_000245.4(MET):c.2265-49G>C

Gene:

MET:MET proto-oncogene, receptor tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000245.4(MET):c.2265-49G>C

HGVS:

NC_000007.14:g.116759342G>C
NG_008996.1:g.91938G>C
NM_000245.4:c.2265-49G>CMANE SELECT
NM_001127500.3:c.2270G>C
NM_001324401.3:c.2265-49G>C
NM_001324402.2:c.975-49G>C
NP_001120972.1:p.Trp757Ser
LRG_662t1:c.2270G>C
LRG_662:g.91938G>C
NC_000007.13:g.116399396G>C
NM_001127500.1:c.2270G>C

Protein change:

W757S

Links:

dbSNP: rs1196543273

NCBI 1000 Genomes Browser:

rs1196543273

Molecular consequence:

NM_000245.4:c.2265-49G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001324401.3:c.2265-49G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001324402.2:c.975-49G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001127500.3:c.2270G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Renal cell carcinoma (RCCP1)
Identifiers:: MONDO: MONDO:0005086; MeSH: D002292; MedGen: C0007134; Human Phenotype Ontology: HP:0005584

Recent activity

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Chaerephon plicatus isolate QW glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ...
Chaerephon plicatus isolate QW glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, partial cds
gi|874528244|gb|KM998631.1|

Nucleotide
Rattus norvegicus leucine rich repeat transmembrane neuronal 4, mRNA (cDNA clone...
Rattus norvegicus leucine rich repeat transmembrane neuronal 4, mRNA (cDNA clone MGC:188202 IMAGE:7319359), complete cds
gi|195539735|gb|BC168219.1|

Nucleotide
LOC103974535 [Musa acuminata AAA Group]
LOC103974535 [Musa acuminata AAA Group]
Gene ID:103974535

Gene
MPH1 [Verticillium nonalfalfae]
MPH1 [Verticillium nonalfalfae]
Gene ID:39603844

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002159010	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2023)	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

SCV002159010

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2023)

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, SCV002159010.3

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

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 757 of the MET protein (p.Trp757Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 1318526). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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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