Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000409717 | SCV000485972 | likely pathogenic | Ataxia-telangiectasia syndrome | 2016-03-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000409717 | SCV001401485 | pathogenic | Ataxia-telangiectasia syndrome | 2023-02-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 370611). This premature translational stop signal has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 24549055, 28779002). This variant is present in population databases (rs754562056, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln1852*) 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). |
Genetics and Molecular Pathology, |
RCV002272217 | SCV002556443 | likely pathogenic | Familial cancer of breast | 2022-05-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002348124 | SCV002649961 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-12-26 | criteria provided, single submitter | clinical testing | The p.Q1852* pathogenic mutation (also known as c.5554C>T), located in coding exon 36 of the ATM gene, results from a C to T substitution at nucleotide position 5554. This changes the amino acid from a glutamine to a stop codon within coding exon 36. This alteration has been identified in a cohort of high-risk breast/ovarian cancer patients and has been reported in at least one subject in a study of 13087 breast cancer cases and 5488 control individuals in the UK (Castéra L et al. Eur. J. Hum. Genet. 2014 Nov;22:1305-13; Decker B et al. J. Med. Genet. 2017 11;54:732-741). This alteration was also reported as an actionable incidental pathological finding in an individual with a family history of female breast and pancreatic cancer and brain tumor from a cohort of 200 individuals with cardiovascular disease undergoing whole exome sequencing (Seidelmann SB et al. Circ Cardiovasc Genet. 2017 Feb;10:). In addition to the information 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. |
Baylor Genetics | RCV002272217 | SCV004210236 | pathogenic | Familial cancer of breast | 2023-06-26 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV002272217 | SCV004930350 | pathogenic | Familial cancer of breast | 2024-01-25 | 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. |
NHS Central & South Genomic Laboratory Hub | RCV005252871 | SCV005907149 | pathogenic | Inherited breast cancer and ovarian cancer | 2025-04-09 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV005355688 | SCV005912536 | pathogenic | ATM-related cancer predisposition | 2022-01-14 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV002348124 | SCV006061483 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-11-05 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 37/63 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 24549055, 28087566, 28779002, 32802943). This variant has been identified in 1/250986 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |