ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2085G>A (p.Leu695=)

gnomAD frequency: 0.00002  dbSNP: rs786202229
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164945 SCV000215634 likely benign Hereditary cancer-predisposing syndrome 2014-07-14 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000232379 SCV000282888 likely benign Ataxia-telangiectasia syndrome 2024-01-30 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000164945 SCV000682024 likely benign Hereditary cancer-predisposing syndrome 2017-03-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589366 SCV000694205 likely benign not specified 2021-07-26 criteria provided, single submitter clinical testing
GeneDx RCV001357303 SCV001828173 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000164945 SCV002534066 likely benign Hereditary cancer-predisposing syndrome 2020-11-09 criteria provided, single submitter curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003491895 SCV004240391 likely benign Breast and/or ovarian cancer 2023-06-22 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001357303 SCV004563635 likely benign not provided 2023-04-28 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004589760 SCV005083860 benign Familial cancer of breast 2024-05-07 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357303 SCV001552732 uncertain significance not provided no assertion criteria provided clinical testing The ATM p.Leu695= variant was identified in 2 of 5526 proband chromosomes (frequency: 0.00018) from individuals or families with breast cancer (Bernstein_2010, Rosenstein_2006). The variant was also identified in dbSNP (ID: rs786202229) as “With Likely benign allele”, ClinVar (as likely benign by Ambry Genetics, Invitae, and Color Genomics and as uncertain significance by Integrated Genetics), and Clinvitae (2x). The variant was not identified in the Cosmic, MutDB, LOVD 3.0, or ATM-LOVD databases. The variant was identified in control databases in 1 of 30948 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). It was observed in the “Other” population in 1 of 980 chromosomes (freq: 0.00102), but not in the African, Latino, European (Non-Finnish), Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The p.Leu695Leu variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. However, 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict the creation of a cryptic 3’ splice site; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Natera, Inc. RCV000232379 SCV002076965 likely benign Ataxia-telangiectasia syndrome 2020-01-23 no assertion criteria provided clinical testing

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