Submissions for variant NM_000051.4(ATM):c.6658C>T (p.Gln2220Ter)

gnomAD frequency: 0.00001  dbSNP: rs1060501536

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000470482	SCV000546675	pathogenic	Ataxia-telangiectasia syndrome	2023-12-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2220*) 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 variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 407464). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000497262	SCV000588893	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-05	criteria provided, single submitter	clinical testing	The p.Q2220* pathogenic mutation (also known as c.6658C>T), located in coding exon 45 of the ATM gene, results from a C to T substitution at nucleotide position 6658. This changes the amino acid from a glutamine to a stop codon within coding exon 45. 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	RCV000497262	SCV000910286	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-25	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 46 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 observed in biallelic individuals affected with ataxia-telangiectasia (PMID: 32095276, 33547824). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001090518	SCV001246115	pathogenic	not provided	2019-06-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003155941	SCV004209525	pathogenic	Familial cancer of breast	2023-08-31	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003155941	SCV004930624	pathogenic	Familial cancer of breast	2024-01-30	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.
Natera, Inc.	RCV000470482	SCV002076687	pathogenic	Ataxia-telangiectasia syndrome	2021-04-07	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV003155941	SCV002588988	pathogenic	Familial cancer of breast	2022-08-26	no assertion criteria provided	clinical testing
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences	RCV000470482	SCV003935149	pathogenic	Ataxia-telangiectasia syndrome		no assertion criteria provided	research