Submissions for variant NM_000051.4(ATM):c.283C>T (p.Gln95Ter)

dbSNP: rs587781545

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129559	SCV000184340	pathogenic	Hereditary cancer-predisposing syndrome	2023-08-30	criteria provided, single submitter	clinical testing	The p.Q95* pathogenic mutation (also known as c.283C>T), located in coding exon 3 of the ATM gene, results from a C to T substitution at nucleotide position 283. This changes the amino acid from a glutamine to a stop codon within coding exon 3. 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	RCV000129559	SCV001339385	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-28	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 4 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 been identified in 1/250948 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194302	SCV001363726	likely pathogenic	Familial cancer of breast	2019-06-06	criteria provided, single submitter	clinical testing	Variant summary: ATM c.283C>T (p.Gln95X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250948 control chromosomes. c.283C>T has been reported in the literature in individuals affected with Breast Cancer (Lu_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857440	SCV002245803	pathogenic	Ataxia-telangiectasia syndrome	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln95*) 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 breast cancer (PMID: 26317927, 26689913). ClinVar contains an entry for this variant (Variation ID: 141167). 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.
Fulgent Genetics, Fulgent Genetics	RCV002492495	SCV002798561	likely pathogenic	Familial cancer of breast; Ataxia-telangiectasia syndrome	2022-05-27	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001194302	SCV004212144	pathogenic	Familial cancer of breast	2022-12-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001194302	SCV004930429	pathogenic	Familial cancer of breast	2024-01-08	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.