Submissions for variant NM_007194.4(CHEK2):c.902del (p.Leu301fs)

dbSNP: rs748005072

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164458	SCV000215101	pathogenic	Hereditary cancer-predisposing syndrome	2021-08-02	criteria provided, single submitter	clinical testing	The c.902delT pathogenic mutation, located in coding exon 7 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 902, causing a translational frameshift with a predicted alternate stop codon (p.L301Wfs*3). 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.
GeneDx	RCV000479231	SCV000567594	pathogenic	not provided	2023-08-17	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.1031delT (p.Leu344TrpfsX3); This variant is associated with the following publications: (PMID: 25330149, 28152038, 31159747, 31036035, 32805687, 29922827, 36493725, 36644613, 33840814, 35441217, 36315097, 33528079)
Counsyl	RCV000576741	SCV000677815	likely pathogenic	Familial cancer of breast	2017-04-11	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000164458	SCV000821731	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-01	criteria provided, single submitter	clinical testing	This variation is a single nucleotide deletion in exon 8 of the CHEK2 mRNA (c.902delT), causing a frameshift at codon 301. This creates a premature stop codon 3 amino acid residues later - p.(Leu301Trpfs*3) - and is expected to result in an absent or disrupted protein product. This variant has been described in the literature in at least one individual with a personal and family history of breast cancer (PMID: 25330149 ). The mutation database ClinVar contains entry for this variant (Variation ID: 185097/).
Color Diagnostics, LLC DBA Color Health	RCV000164458	SCV000904453	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 8 of the CHEK2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/204874 chromosomes 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	RCV000576741	SCV000933492	pathogenic	Familial cancer of breast	2023-12-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu301Trpfs*3) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 25330149). ClinVar contains an entry for this variant (Variation ID: 185097). For these reasons, this variant has been classified as Pathogenic.
Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf	RCV000164458	SCV001482301	uncertain significance	Hereditary cancer-predisposing syndrome		criteria provided, single submitter	research
MGZ Medical Genetics Center	RCV000576741	SCV002580887	likely pathogenic	Familial cancer of breast	2022-06-20	criteria provided, single submitter	clinical testing
Human Genetics Bochum, Ruhr University Bochum	RCV002463654	SCV002758599	likely pathogenic	Colorectal cancer	2022-03-28	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PVS1, PM2
CeGaT Center for Human Genetics Tuebingen	RCV000479231	SCV004011386	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	CHEK2: PVS1, PM2, PS4:Supporting
Myriad Genetics, Inc.	RCV000576741	SCV004020135	pathogenic	Familial cancer of breast	2023-03-08	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.