Submissions for variant NM_000051.4(ATM):c.5910del (p.Glu1971fs)

dbSNP: rs587782198

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130858	SCV000185757	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-15	criteria provided, single submitter	clinical testing	The c.5910delA pathogenic mutation, located in coding exon 38 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 5910, causing a translational frameshift with a predicted alternate stop codon (p.E1971Rfs*19). This mutation was reported in conjunction with a second truncating mutation in a British ataxia-telangiectasia (AT) patient (Stankovic T et al. Am. J. Hum. Genet. 1998 Feb;62:334-45) and was detected in 2/13087 breast cancer cases and 0/5488 control individuals in the UK (Decker B et al. J. Med. Genet. 2017 Nov;54:732-741). 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.
GeneDx	RCV000480849	SCV000568327	pathogenic	not provided	2019-12-17	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 in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9463314, 27433846, 15928302, 28779002)
Counsyl	RCV000576813	SCV000678093	likely pathogenic	Ataxia-telangiectasia syndrome	2017-01-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576813	SCV000816559	pathogenic	Ataxia-telangiectasia syndrome	2024-12-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1971Argfs*19) 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 premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 9463314, 15928302, 27433846, 28779002). ClinVar contains an entry for this variant (Variation ID: 142051). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000130858	SCV001347418	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 39 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.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000130858	SCV001448950	pathogenic	Hereditary cancer-predisposing syndrome	2019-12-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003467157	SCV004210193	pathogenic	Familial cancer of breast	2024-03-16	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003467157	SCV004932857	pathogenic	Familial cancer of breast	2024-01-26	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.