Submissions for variant NM_007194.4(CHEK2):c.216T>G (p.Tyr72Ter)

dbSNP: rs587781705

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129876	SCV000184693	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-29	criteria provided, single submitter	clinical testing	The p.Y72* pathogenic mutation (also known as c.216T>G), located in coding exon 1 of the CHEK2 gene, results from a T to G substitution at nucleotide position 216. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. This mutation has been reported in a patient with renal cancer (Mandelker D et al. JAMA 2017 09;318(9):825-835). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics	RCV000763478	SCV000894260	pathogenic	Familial cancer of breast; Li-Fraumeni syndrome 2; Bone osteosarcoma; Malignant tumor of prostate	2018-10-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129876	SCV000911686	pathogenic	Hereditary cancer-predisposing syndrome	2021-03-01	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 2 of the CHEK2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CHEK2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Invitae	RCV001247758	SCV001421199	pathogenic	Familial cancer of breast	2023-12-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr72*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with renal cell carcinoma (PMID: 29978187). ClinVar contains an entry for this variant (Variation ID: 141381). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV001247758	SCV004043282	pathogenic	Familial cancer of breast	2023-06-22	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.