Submissions for variant NM_000051.4(ATM):c.5405dup (p.His1802fs)

dbSNP: rs1555106452

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000539153	SCV000622585	pathogenic	Ataxia-telangiectasia syndrome	2021-02-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant has been reported in the literature in a family affected with ataxia-telangiectasia (PMID: 10980530). This variant is also known as 5405-5406insA in the literature. ClinVar contains an entry for this variant (Variation ID: 453575). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.His1802Glnfs*2) in the ATM gene. It is expected to result in an absent or disrupted protein product.
Color Diagnostics, LLC DBA Color Health	RCV000776817	SCV000912472	pathogenic	Hereditary cancer-predisposing syndrome	2020-04-24	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 36 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 been reported in an individual affected with ataxia telangiectasia (PMID: 10980530). 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.
Ambry Genetics	RCV000776817	SCV002651476	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-07	criteria provided, single submitter	clinical testing	The c.5405dupA pathogenic mutation, located in coding exon 35 of the ATM gene, results from a duplication of A at nucleotide position 5405, causing a translational frameshift with a predicted alternate stop codon (p.H1802Qfs*2). This alteration has been detected in the compound heterozygous state in a Danish individual with ataxia-telangiectasia (Laake K et al. Hum. Mutat., 2000 Sep;16:232-46). 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.
Myriad Genetics, Inc.	RCV004023648	SCV004933853	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.