Submissions for variant NM_000051.4(ATM):c.8695dup (p.Ile2899fs)

dbSNP: rs1555142816

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657337	SCV000779069	pathogenic	not provided	2017-06-12	criteria provided, single submitter	clinical testing	This duplication of one nucleotide in ATM is denoted c.8695dupA at the cDNA level and p.Ile2899AsnfsX6 (I2899NfsX6) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAAA[dupA]TCCT. The duplication causes a frameshift which changes an Isoleucine to an Asparagine at codon 2899, and creates a premature stop codon at position 6 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this duplication to be pathogenic.
Invitae	RCV001234056	SCV001406682	pathogenic	Ataxia-telangiectasia syndrome	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile2899Asnfs*6) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 545794). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002369777	SCV002684125	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-01	criteria provided, single submitter	clinical testing	The c.8695dupA pathogenic mutation, located in coding exon 59 of the ATM gene, results from a duplication of A at nucleotide position 8695, causing a translational frameshift with a predicted alternate stop codon (p.I2899Nfs*6). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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	RCV003459557	SCV004216236	likely pathogenic	Familial cancer of breast	2021-05-28	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003459557	SCV004931626	pathogenic	Familial cancer of breast	2024-02-05	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.