ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4820del (p.Pro1607fs)

dbSNP: rs2135834949
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV001823011 SCV002072499 likely pathogenic Familial cancer of breast 2022-02-01 criteria provided, single submitter clinical testing The variant c.4820del (p.(Pro1607Hisfs*2)) in exon 32 of the ATM-gene is not found in the gnomAD database, it creates a frame shift starting at codon Pro1607. The new reading frame ends in a STOP codon at position 2. Frameshift variants leading to a loss of function of ATM protein are a known mechanism of disease. ACMG criteria used for classification: PVS1, PM2.
Ambry Genetics RCV002334715 SCV002635047 pathogenic Hereditary cancer-predisposing syndrome 2022-03-21 criteria provided, single submitter clinical testing The c.4820delC pathogenic mutation, located in coding exon 31 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 4820, causing a translational frameshift with a predicted alternate stop codon (p.P1607Hfs*2). This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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