ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7010_7065dup (p.Ile2356delinsValTer)

dbSNP: rs1555120985
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000295592 SCV000330737 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing This duplication of 56 nucleotides in ATM is denoted c.7010_7065dup56 at the cDNA level and p.Ile2356ValfsX2 (I2356VfsX2) at the protein level. The surrounding sequence is GAAT[dup56]ATCA. The duplication causes a frameshift which changes an Isoleucine to a Valine at codon 2356, and creates a premature stop codon at position 2 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.7010_7065dup56 was reported in two siblings with pancreatic cancer from a kindred with pancreatic, colon, breast, and other cancer diagnoses (Barnes 2017). Based on the currently available information, we consider this duplication to be pathogenic.
Ambry Genetics RCV002365292 SCV002666795 pathogenic Hereditary cancer-predisposing syndrome 2022-06-16 criteria provided, single submitter clinical testing The c.7010_7065dup56 variant, located in coding exon 47 of the ATM gene, results from a duplication of GTCTGAGGGTTTGTGGCAACTGGTTAGCAGAAACGTGCTTAGAAAATCCTGCGGTC at nucleotide positions 7010 to 7065, causing a translational frameshift with a predicted alternate stop codon (p.I2356Vfs*2). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002519063 SCV003312405 pathogenic Ataxia-telangiectasia syndrome 2022-12-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280787). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile2356Valfs*2) 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).

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