Submissions for variant NM_000051.4(ATM):c.8911C>T (p.Gln2971Ter)

dbSNP: rs1565607653

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000706912	SCV000835987	pathogenic	Ataxia-telangiectasia syndrome	2022-11-23	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: 582761). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 26628246). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln2971*) 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).
Color Diagnostics, LLC DBA Color Health	RCV000773913	SCV000907613	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 62 of the ATM gene, creating a 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.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001258065	SCV001434896	likely pathogenic	Ataxia-telangiectasia syndrome; Breast cancer, susceptibility to	2019-12-30	criteria provided, single submitter	clinical testing	This c.8911C>T (p.Gln2971Ter) variant in exon 62 of the ATM gene creates a premature translational stop signal and is predicted to disrupt protein function either through nonsense-mediated decay or protein truncation. This variant is not present in population databases (gnomAD). This variant has been reported in combination with another ATM loss-of-function variant in a Chinese individual affected with autosomal recessive ataxia-telangiectasia (PMID: 26628246). Individuals who are heterozygous for a pathogenic ATM variant are at increased risk for cancer, in particular breast cancer in women. This variant is classified as likely pathogenic.
Ambry Genetics	RCV000773913	SCV002685570	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-09	criteria provided, single submitter	clinical testing	The p.Q2971* pathogenic mutation (also known as c.8911C>T), located in coding exon 61 of the ATM gene, results from a C to T substitution at nucleotide position 8911. This changes the amino acid from a glutamine to a stop codon within coding exon 61. This alteration has been detected with a protein-truncating mutation in trans in an individual diagnosed with ataxia telangiectasia (Liu XL et al. Neurosci Lett, 2016 Jan;611:112-5). 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.
Baylor Genetics	RCV003460987	SCV004216215	pathogenic	Familial cancer of breast	2021-08-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003460987	SCV004933715	pathogenic	Familial cancer of breast	2024-02-06	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.