Submissions for variant NM_000051.4(ATM):c.7220C>A (p.Ser2407Ter)

dbSNP: rs1555122149

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000627953	SCV000748839	pathogenic	Ataxia-telangiectasia syndrome	2023-04-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2407*) 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 524287). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32427313). This variant is not present in population databases (gnomAD no frequency).
Color Diagnostics, LLC DBA Color Health	RCV001185806	SCV001352111	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-07	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 49 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with breast and colorectal cancer (PMID: 32792570). 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.
Ambry Genetics	RCV001185806	SCV002670232	pathogenic	Hereditary cancer-predisposing syndrome	2024-10-14	criteria provided, single submitter	clinical testing	The p.S2407* pathogenic mutation (also known as c.7220C>A), located in coding exon 48 of the ATM gene, results from a C to A substitution at nucleotide position 7220. This changes the amino acid from a serine to a stop codon within coding exon 48. 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.
Baylor Genetics	RCV003465370	SCV004212066	pathogenic	Familial cancer of breast	2023-03-11	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003465370	SCV004931245	pathogenic	Familial cancer of breast	2024-01-31	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.