Submissions for variant NM_000051.4(ATM):c.3403-15T>A

gnomAD frequency: 0.02975  dbSNP: rs79701258

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123741	SCV000167084	benign	not specified	2014-01-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000373309	SCV000367046	likely benign	Ataxia-telangiectasia syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Color Diagnostics, LLC DBA Color Health	RCV000447892	SCV000537395	benign	Hereditary cancer-predisposing syndrome	2015-04-08	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000373309	SCV000743726	likely benign	Ataxia-telangiectasia syndrome	2014-10-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000373309	SCV001750397	benign	Ataxia-telangiectasia syndrome	2021-07-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798413	SCV002042115	benign	Breast and/or ovarian cancer	2021-04-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000447892	SCV002618386	benign	Hereditary cancer-predisposing syndrome	2014-07-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000123741	SCV002760559	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315835	SCV004016003	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000123741	SCV004102504	benign	not specified	2023-11-12	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000373309	SCV000745811	benign	Ataxia-telangiectasia syndrome	2017-09-27	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000373309	SCV001457144	benign	Ataxia-telangiectasia syndrome	2020-09-16	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357621	SCV001553142	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM c.3403-15T>A variant was not identified in the literature nor was it identified in the Cosmic, MutDB, databases. The variant was identified in dbSBP (ID: rs79701258) as “With Likely benign allele,” ClinVar (as likely benign by Ilumina and as benign by GeneDx and Color Genomics), Clinvitae, and ATM-LOVD databases. The variant was identified in control databases in 3007 of 258930 chromosomes at a frequency of 0.011613 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the African population at a frequency greater than 1% in 2265 (109 homozygous) of 23444 chromosomes (freq: 0.097), and at lower frequencies in the following populations: Other in 29 of 5964 chromosomes (freq. 0.005), Latino in 198 (1 homozygous) of 31316 chromosomes (freq. 0.006), European (Non-Finnish) in 104 of 119980 chromosomes (freq. 0.0009), Ashkenazi Jewish in 1 of 9232 chromosomes (freq. 0.0001), East Asian in 158 of 18072 (freq. 0.0087), European (Finnish) in 8 of 24280 chromosomes (freq. 0.0003) and South Asian in 244 (1 homozygous) of 26642 chromosomes (freq. 0.009), increasing the likelihood this could be a low frequency benign variant. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000123741	SCV001906044	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000123741	SCV001924545	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000123741	SCV002036581	benign	not specified		no assertion criteria provided	clinical testing