Submissions for variant NM_000051.4(ATM):c.2467-7C>T

gnomAD frequency: 0.00001  dbSNP: rs768850329

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080098	SCV000282902	likely benign	Ataxia-telangiectasia syndrome	2024-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000587579	SCV000512145	likely benign	not provided	2019-10-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579933	SCV000682059	likely benign	Hereditary cancer-predisposing syndrome	2017-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005406973	SCV000694224	likely benign	not specified	2025-04-17	criteria provided, single submitter	clinical testing	Variant summary: ATM c.2467-7C>T alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 251102 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2467-7C>T in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 236691). Based on the evidence outlined above, the variant was classified as likely benign.
Sema4, Sema4	RCV000579933	SCV002532200	uncertain significance	Hereditary cancer-predisposing syndrome	2021-05-17	criteria provided, single submitter	curation
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587579	SCV004565150	likely benign	not provided	2023-08-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004591050	SCV005084662	benign	Familial cancer of breast	2024-05-09	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354655	SCV001549321	uncertain significance	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM c.2467-7C>T variant was not identified in the literature nor was it identified in the COGR, Cosmic, LOVD 3.0, or the ATM-LOVD database. The variant was identified in dbSNP (ID: rs768850329) as "With Uncertain significance allele", and in ClinVar (classified as likely benign by Invitae, GeneDx, Color Genomics; as uncertain significance by Integrated Genetics/Laboratory Corporation of America). The variant was identified in control databases in 5 of 245888 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European Non-Finnish in 3 of 111516 chromosomes (freq: 0.00003), and Ashkenazi Jewish in 2 of 9834 chromosomes (freq: 0.0002); it was not observed in the African, Other, Latino, East Asian, Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and 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. This variant is classified as a variant of uncertain significance.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000587579	SCV001808739	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000587579	SCV001953737	likely benign	not provided		no assertion criteria provided	clinical testing