ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8395_8404delTTTCAGTGCC (p.Phe2799Lysfs) (rs786202800)

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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 RCV000165801 SCV000216548 pathogenic Hereditary cancer-predisposing syndrome 2017-04-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000165801 SCV000687827 pathogenic Hereditary cancer-predisposing syndrome 2016-05-03 criteria provided, single submitter clinical testing
Counsyl RCV000204163 SCV000678030 likely pathogenic Ataxia-telangiectasia syndrome 2015-10-13 criteria provided, single submitter clinical testing
GeneDx RCV000255017 SCV000321412 pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing This deletion of 10 nucleotides in ATM is denoted c.8395_8404del10 at the cDNA level and p.Phe2799LysfsX4 (F2799KfsX4) at the protein level. The surrounding sequence is TGCC[del10]AAAAG. The deletion causes a frameshift, which changes a Phenylalanine to a Lysine at codon 2799, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.8395_8404del10, also published as 8395del10, has been observed in multiple individuals with Ataxia-telangiectasia as well as two individuals with pancreatic cancer and another with young onset colon cancer (Broeks 1998, Sandoval 1999, Li 2000, Mitui 2003, Ehlayel 2008, Carney 2012, Pearlman 2017, Shindo 2017). Based on currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000204163 SCV000260589 pathogenic Ataxia-telangiectasia syndrome 2018-07-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe2799Lysfs*4) in the ATM gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with ataxia-telangiectasia (PMID: 9887333, 9792409, 10817650, 12815592, 21833744), and colorectal cancer (PMID: 25980754, 27978560). This variant is also known as 839del10 in the literature. ClinVar contains an entry for this variant (Variation ID: 186242). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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