Submissions for variant NM_000051.4(ATM):c.6730dup (p.Arg2244fs)

dbSNP: rs1060501543

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478857	SCV000571332	likely pathogenic	not provided	2016-08-15	criteria provided, single submitter	clinical testing	This duplication of one nucleotide in ATM is denoted c.6730dupA at the cDNA level and p.Arg2244LysfsX5 (R2244KfsX5) at the protein level. The normal sequence, with the base that is duplicated in braces, is ACAA[A]GAGA. The duplication causes a frameshift which changes an Arginine to a Lysine at codon 2244, and creates a premature stop codon at position 5 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 a likely pathogenic variant.
Myriad Genetics, Inc.	RCV003139681	SCV003806683	pathogenic	Familial cancer of breast	2023-01-13	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics	RCV004023162	SCV005019051	pathogenic	Hereditary cancer-predisposing syndrome	2023-10-30	criteria provided, single submitter	clinical testing	The c.6730dupA pathogenic mutation, located in coding exon 45 of the ATM gene, results from a duplication of A at nucleotide position 6730, causing a translational frameshift with a predicted alternate stop codon (p.R2244Kfs*5). 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.