Submissions for variant NM_000051.4(ATM):c.850C>T (p.Gln284Ter)

dbSNP: rs757782702

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000493159	SCV000581449	pathogenic	Hereditary cancer-predisposing syndrome	2019-03-12	criteria provided, single submitter	clinical testing	The p.Q284* pathogenic mutation (also known as c.850C>T), located in coding exon 6 of the ATM gene, results from a C to T substitution at nucleotide position 850. This changes the amino acid from a glutamine to a stop codon within coding exon 6. 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	RCV000493159	SCV000913535	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-26	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 7 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, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250056 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001389991	SCV001591559	pathogenic	Ataxia-telangiectasia syndrome	2021-12-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 429069). This premature translational stop signal has been observed in individual(s) with pancreatic cancer (PMID: 31285527). This variant is present in population databases (rs757782702, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln284*) 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).
Baylor Genetics	RCV003470607	SCV004210269	likely pathogenic	Familial cancer of breast	2023-06-19	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470607	SCV004930419	pathogenic	Familial cancer of breast	2024-01-11	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.