Submissions for variant NM_000051.4(ATM):c.6049dup (p.Ser2017fs)

dbSNP: rs797045030

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV000191063	SCV000245453	pathogenic	Ataxia-telangiectasia syndrome	2014-09-22	criteria provided, single submitter	clinical testing	This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in trans with a pathogenic variant [V2424G] in a 27-year-old female with ataxia and elevated AFP
Labcorp Genetics (formerly Invitae), Labcorp	RCV000191063	SCV000547024	pathogenic	Ataxia-telangiectasia syndrome	2023-02-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2017Lysfs*16) 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: 209134). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000575568	SCV000665429	pathogenic	Hereditary cancer-predisposing syndrome	2021-11-12	criteria provided, single submitter	clinical testing	The c.6049dupA pathogenic mutation, located in coding exon 40 of the ATM gene, results from a duplication of A at nucleotide position 6049, causing a translational frameshift with a predicted alternate stop codon (p.S2017Kfs*16). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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	RCV000575568	SCV000903396	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 41 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	RCV003468879	SCV004207092	pathogenic	Familial cancer of breast	2024-02-26	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003468879	SCV004931854	pathogenic	Familial cancer of breast	2024-01-29	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.