ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.640del (p.Ser214fs) (rs786204543)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169254 SCV000220538 likely pathogenic Ataxia-telangiectasia syndrome 2014-07-23 criteria provided, single submitter literature only
GeneDx RCV000494401 SCV000581706 pathogenic not provided 2018-04-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.640delT at the cDNA level and p.Ser214ProfsX16 (S214PfsX16) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTTTTTT[delT]CCAA. The deletion causes a frameshift which changes a Serine to a Proline at codon 214, and creates a premature stop codon at position 16 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM Ser214ProfsX16 is reported to be a Spanish founder variant and has been observed in both individuals with ataxia telangiectasia and breast cancer (Byrd 1996, Mitui 2003, Coutinho 2004, Demuth 2011, Carranza 2017, Tavera-Tapia 2017). We consider this variant to be pathogenic.
Ambry Genetics RCV000561764 SCV000672614 pathogenic Hereditary cancer-predisposing syndrome 2018-05-11 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000169254 SCV000748987 pathogenic Ataxia-telangiectasia syndrome 2019-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser214Profs*16) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the homozygous and compound heterozygous states in several individuals affected with ataxia-telangiectasia (PMID: 8789452, 21965147, 12815592, 15039971). It has also been observed in the heterozygous state in individuals affected with breast cancer or referred for cancer panel testing (PMID: 21445571, 26681312). ClinVar contains an entry for this variant (Variation ID: 188895). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000169254 SCV000838473 pathogenic Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000561764 SCV001342222 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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