ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5554C>T (p.Gln1852Ter)

dbSNP: rs754562056
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Total submissions: 9
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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 (formerly Invitae), Labcorp 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, SA 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, Inc. 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, Sinai Health System RCV005355688 SCV005912536 pathogenic ATM-related cancer predisposition 2022-01-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health 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.

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