Submissions for variant NM_000051.4(ATM):c.7699_7702del (p.Asn2567fs)

dbSNP: rs1060501547

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000463805	SCV000546691	pathogenic	Ataxia-telangiectasia syndrome	2023-12-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn2567Glufs*5) 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: 407478). 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.
GeneDx	RCV000486343	SCV000572199	likely pathogenic	not provided	2023-08-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with acute myeloid leukaemia in published literature (Lu et al., 2015); This variant is associated with the following publications: (PMID: 26689913, 36451132, 35047863)
Ambry Genetics	RCV001026721	SCV001189158	pathogenic	Hereditary cancer-predisposing syndrome	2019-06-20	criteria provided, single submitter	clinical testing	The c.7699_7702delAACA pathogenic mutation, located in coding exon 51 of the ATM gene, results from a deletion of 4 nucleotides at nucleotide positions 7699 to 7702, causing a translational frameshift with a predicted alternate stop codon (p.N2567Efs*5). 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	RCV001026721	SCV001341164	pathogenic	Hereditary cancer-predisposing syndrome	2020-03-21	criteria provided, single submitter	clinical testing	This variant deletes 4 nucleotides in exon 52 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. 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000486343	SCV004027250	likely pathogenic	not provided	2023-08-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003470415	SCV004212118	likely pathogenic	Familial cancer of breast	2023-01-10	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470415	SCV004931855	pathogenic	Familial cancer of breast	2024-01-31	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.