Submissions for variant NM_000051.4(ATM):c.6013delinsAA (p.Leu2005fs)

dbSNP: rs1555113523

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520231	SCV000617108	likely pathogenic	not provided	2017-03-08	criteria provided, single submitter	clinical testing	This combined deletion and insertion is denoted ATM c.6013delCinsAA at the cDNA level and p.Leu2005AsnfsX13 (L2005NfsX13) at the protein level. The surrounding sequence, with the bases that are deleted and inserted in brackets, is TCTT[delC][insAA]TCTT. The variant causes a frameshift, which changes a Leucine to an Asparagine at codon 2005, and creates a premature stop codon at position 13 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 currently available information, we consider this to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001245852	SCV001419171	pathogenic	Ataxia-telangiectasia syndrome	2022-08-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with endometrial cancer (PMID: 30612635). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu2005Asnfs*13) 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).
Ambry Genetics	RCV002358406	SCV002656607	pathogenic	Hereditary cancer-predisposing syndrome	2017-02-17	criteria provided, single submitter	clinical testing	The c.6013delCinsAA pathogenic mutation, located in coding exon 40 of the ATM gene, results from the deletion of one nucleotide and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.L2005Nfs*13). 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.
Myriad Genetics, Inc.	RCV004023538	SCV004933573	pathogenic	Familial cancer of breast	2024-01-26	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.