Submissions for variant NM_000051.4(ATM):c.5658T>C (p.Pro1886=)

gnomAD frequency: 0.00001  dbSNP: rs940182945

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000988697	SCV000558426	likely benign	Ataxia-telangiectasia syndrome	2024-10-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000568664	SCV000660639	likely benign	Hereditary cancer-predisposing syndrome	2016-06-21	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.
Color Diagnostics, LLC DBA Color Health	RCV000568664	SCV000682278	likely benign	Hereditary cancer-predisposing syndrome	2017-04-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000613337	SCV000732609	likely benign	not specified	2017-06-13	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.
Mendelics	RCV000988697	SCV001138526	likely benign	Ataxia-telangiectasia syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000568664	SCV002529068	likely benign	Hereditary cancer-predisposing syndrome	2021-06-25	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000613337	SCV005076145	likely benign	not specified	2024-04-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004591389	SCV005085083	benign	Familial cancer of breast	2024-05-23	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	RCV001357771	SCV001553340	likely benign	not provided		no assertion criteria provided	clinical testing	The ATM p.Pro1886= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs940182945) as “With Likely benign allele” and ClinVar (classified as likely benign by Invitae, Ambry Genetics, Color and GeneDx). The variant was identified in control databases in 2 of 245570 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the African population in 2 of 15268 chromosomes (freq: 0.0001), while not observed in the Other, Latino, European Non-Finnish, Ashkenazi Jewish, East Asian, European Finnish, or South Asian populations. The p.Pro1886= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004551552	SCV004758062	likely benign	ATM-related disorder	2020-03-19	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).