Submissions for variant NM_000051.4(ATM):c.6181C>T (p.Gln2061Ter)

dbSNP: rs1555113845

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000583766	SCV000687678	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-26	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 42 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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	RCV000583766	SCV001187077	pathogenic	Hereditary cancer-predisposing syndrome	2018-05-21	criteria provided, single submitter	clinical testing	The p.Q2061* pathogenic mutation (also known as c.6181C>T), located in coding exon 41 of the ATM gene, results from a C to T substitution at nucleotide position 6181. This changes the amino acid from a glutamine to a stop codon within coding exon 41. 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.
Invitae	RCV001381514	SCV001579947	pathogenic	Ataxia-telangiectasia syndrome	2023-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2061*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 490641). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV004024639	SCV004931288	pathogenic	Familial cancer of breast	2024-01-29	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.