Submissions for variant NM_000051.4(ATM):c.3939_3940del (p.Glu1313fs)

dbSNP: rs1555093684

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000667702	SCV000792195	likely pathogenic	Ataxia-telangiectasia syndrome	2017-06-09	criteria provided, single submitter	clinical testing
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV000709712	SCV000839887	likely pathogenic	Familial cancer of breast	2017-12-24	criteria provided, single submitter	clinical testing	This c.3939_3940delGA (p.Glu1313Aspfs*7) variant in the ATM gene is predicted to introduce a premature translation termination codon. This variant has been observed in a patient with pancreatic cancer (PMID 27449771). Mono-allelic variants in the ATM gene have been associated with susceptibility to breast cancer (OMIM 114480) whereas bi-allelic variants in this gene are associated with Ataxia-telangiectasia (OMIM 208900). This frameshift variant in the ATM gene is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000667702	SCV001217006	pathogenic	Ataxia-telangiectasia syndrome	2024-04-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1313Aspfs*7) 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 premature translational stop signal has been observed in individual(s) with pancreatic cancer (PMID: 27449771). ClinVar contains an entry for this variant (Variation ID: 552442). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000709712	SCV001339139	likely pathogenic	Familial cancer of breast	2020-03-26	criteria provided, single submitter	clinical testing	Variant summary: ATM c.3939_3940delGA (p.Glu1313AspfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251244 control chromosomes (gnomAD). c.3939_3940delGA has been reported in the literature in an individual affected with pancreatic cancer (Yang_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Myriad Genetics, Inc.	RCV000709712	SCV003806656	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	RCV004948559	SCV005503878	pathogenic	Hereditary cancer-predisposing syndrome	2024-10-11	criteria provided, single submitter	clinical testing	The c.3939_3940delGA pathogenic mutation, located in coding exon 25 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 3939 to 3940, causing a translational frameshift with a predicted alternate stop codon (p.E1313Dfs*7). 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.