Submissions for variant NM_000051.4(ATM):c.5203dup (p.Thr1735fs)

gnomAD frequency: 0.00001  dbSNP: rs878853518

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231244	SCV000282982	pathogenic	Ataxia-telangiectasia syndrome	2023-05-20	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 236731). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1735Asnfs*14) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).
Ambry Genetics	RCV001023721	SCV001185636	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-01	criteria provided, single submitter	clinical testing	The c.5203dupA pathogenic mutation, located in coding exon 34 of the ATM gene, results from a duplication of A at nucleotide position 5203, causing a translational frameshift with a predicted alternate stop codon (p.T1735Nfs*14). This alteration was identified in 1/10030 consecutive patients referred for evaluation by an NGS hereditary cancer panel (Susswein LR et al. Genet Med, 2016 08;18:823-32). 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.
Color Diagnostics, LLC DBA Color Health	RCV001023721	SCV001355344	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 35 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV003463630	SCV004207768	likely pathogenic	Familial cancer of breast	2023-08-12	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003463630	SCV004931159	pathogenic	Familial cancer of breast	2024-01-25	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001795357	SCV002035029	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001795357	SCV002037947	pathogenic	not provided		no assertion criteria provided	clinical testing