Submissions for variant NM_000051.4(ATM):c.4252_4259dup (p.Ala1421fs)

dbSNP: rs1591662606

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001022146	SCV001183846	pathogenic	Hereditary cancer-predisposing syndrome	2024-03-21	criteria provided, single submitter	clinical testing	The c.4252_4259dupATTCTTCT pathogenic mutation, located in coding exon 28 of the ATM gene, results from a duplication of ATTCTTCT at nucleotide position 4252, causing a translational frameshift with a predicted alternate stop codon (p.A1421Ffs*33). 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.
Color Diagnostics, LLC DBA Color Health	RCV001022146	SCV004360975	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-07	criteria provided, single submitter	clinical testing	This variant inserts 8 nucleotides in exon 29 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003769555	SCV004656005	pathogenic	Ataxia-telangiectasia syndrome	2022-12-22	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: 824725). 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.Ala1421Phefs*33) 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).
Myriad Genetics, Inc.	RCV004030817	SCV004930358	pathogenic	Familial cancer of breast	2024-01-23	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.