Submissions for variant NM_000051.4(ATM):c.2023C>T (p.Gln675Ter)

gnomAD frequency: 0.00001  dbSNP: rs777849257

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215540	SCV000275934	pathogenic	Hereditary cancer-predisposing syndrome	2024-06-11	criteria provided, single submitter	clinical testing	The p.Q675* pathogenic mutation (also known as c.2023C>T), located in coding exon 12 of the ATM gene, results from a C to T substitution at nucleotide position 2023. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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	RCV000255863	SCV000322534	pathogenic	not provided	2024-04-16	criteria provided, single submitter	clinical testing	Nonsense 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; Observed in individuals with breast or prostate cancer (PMID: 36446039, 32832836, 29922827); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 36446039, 32832836, 29922827, 32427313)
Counsyl	RCV000411314	SCV000487230	likely pathogenic	Ataxia-telangiectasia syndrome	2016-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000411314	SCV000829660	pathogenic	Ataxia-telangiectasia syndrome	2023-11-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln675*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is present in population databases (rs777849257, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 231933). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000255863	SCV001447816	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001293971	SCV001482694	pathogenic	Familial cancer of breast	2024-03-05	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001293971	SCV004933426	pathogenic	Familial cancer of breast	2024-01-17	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.
Laboratory of Urology, Hospital Clinic de Barcelona	RCV003332147	SCV004040581	pathogenic	Malignant tumor of urinary bladder		no assertion criteria provided	research