Submissions for variant NM_000051.4(ATM):c.8761dup (p.Thr2921fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002881389	SCV003238779	pathogenic	Ataxia-telangiectasia syndrome	2022-09-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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.Thr2921Asnfs*4) 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).
Neuberg Centre For Genomic Medicine, NCGM	RCV004786760	SCV005401043	likely pathogenic	Familial cancer of breast	2023-06-22	criteria provided, single submitter	clinical testing	The frameshift variant c.8761dup(p.Thr2921AsnfsTer4) in ATM gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant is absent in gnomAD exomes database. This variant has been submitted to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Threonine 2921, changes this amino acid to Asparagine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Thr2921AsnfsTer4. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (Podralska et. al,, 2014). For these reasons, this variant has been classified as Likely Pathogenic.