NM_000245.4(MET):c.2265-18del AND Renal cell carcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 5, 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:: RCV002004742.6

Allele description [Variation Report for NM_000245.4(MET):c.2265-18del]

NM_000245.4(MET):c.2265-18del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000245.4(MET):c.2265-18del

HGVS:

NC_000007.14:g.116759373del
NG_008996.1:g.91969del
NM_000245.4:c.2265-18delMANE SELECT
NM_001127500.3:c.2301del
NM_001324401.3:c.2265-18del
NM_001324402.2:c.975-18del
NP_001120972.1:p.Leu768fs
LRG_662:g.91969del
NC_000007.13:g.116399424del
NC_000007.13:g.116399427del

Protein change:

L768fs

Links:

dbSNP: rs761305394

NCBI 1000 Genomes Browser:

rs761305394

Molecular consequence:

NM_001127500.3:c.2301del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000245.4:c.2265-18del - intron variant - [Sequence Ontology: SO:0001627]
NM_001324401.3:c.2265-18del - intron variant - [Sequence Ontology: SO:0001627]
NM_001324402.2:c.975-18del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002231403	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 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

SCV002231403

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 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	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, SCV002231403.4

#	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1450021). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (rs761305394, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Leu768Tyrfs*11) in the MET gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MET cause disease.

#	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

ClinVar

Relating variation to medicine