ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8185C>T (p.Gln2729Ter) (rs587781967)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130347 SCV000185198 pathogenic Hereditary cancer-predisposing syndrome 2018-10-09 criteria provided, single submitter clinical testing The p.Q2729* pathogenic mutation (also known as c.8185C>T), located in coding exon 55 of the ATM gene, results from a C to T substitution at nucleotide position 8185. This changes the amino acid from a glutamine to a stop codon within coding exon 55. This pathogenic mutation has been detected in the homozygous state in an individual of Iberian origin with ataxia-telangiectasia (Mitui M et al. Hum. Mutat. 2003 Jul;22:43-50). This pathogenic mutation has also been reported in two unrelated Palestinian women diagnosed with breast cancer at age 39 and 54 (Lolas Hamameh S et al. Int. J. Cancer. 2017 08;141:750-756). The p.Q2729* pathogenic mutation was reported in two unrelated individuals in their 70s diagnosed with pancreatic cancer and a cholangioma, respectively (Shindo K et al. J. Clin. Oncol. 2017 Oct;35:3382-3390). 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.
Counsyl RCV000410300 SCV000486531 likely pathogenic Ataxia-telangiectasia syndrome 2016-06-23 criteria provided, single submitter clinical testing
GeneDx RCV000657613 SCV000779355 pathogenic not provided 2016-07-07 criteria provided, single submitter clinical testing This variant is denoted ATM c.8185C>T at the cDNA level and p.Gln2729Ter (Q2729X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the homozygous state in an individual with classic ataxia-telangiectasia (Mitui 2003). This variant is considered pathogenic.
Invitae RCV000410300 SCV000835581 pathogenic Ataxia-telangiectasia syndrome 2020-03-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2729*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587781967, ExAC 0.002%). This variant has been reported to be homozygous in individuals affected with ataxia-telangiectasia (PMID: 12815592, 24789685). ClinVar contains an entry for this variant (Variation ID: 141726). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV000130347 SCV000911669 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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