Submissions for variant NM_000051.4(ATM):c.5511_5512del (p.Phe1837fs)

dbSNP: rs1555107263

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000550809	SCV000622597	pathogenic	Ataxia-telangiectasia syndrome	2017-04-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). This sequence change deletes 2 nucleotides from exon 37 of the ATM mRNA (c.5511_5512delTT), causing a frameshift at codon 1837. This creates a premature translational stop signal (p.Phe1837Leufs*11) and is expected to result in an absent or disrupted protein product.
Color Diagnostics, LLC DBA Color Health	RCV000777221	SCV000912912	pathogenic	Hereditary cancer-predisposing syndrome	2020-04-24	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 37 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Ambry Genetics	RCV000777221	SCV001186185	pathogenic	Hereditary cancer-predisposing syndrome	2019-02-09	criteria provided, single submitter	clinical testing	The c.5511_5512delTT pathogenic mutation, located in coding exon 36 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 5511 to 5512, causing a translational frameshift with a predicted alternate stop codon (p.F1837Lfs*11). 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.
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV001030598	SCV001193483	likely pathogenic	Hereditary breast ovarian cancer syndrome	2019-05-01	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000550809	SCV001360468	likely pathogenic	Ataxia-telangiectasia syndrome	2019-04-26	criteria provided, single submitter	clinical testing	Variant summary: ATM c.5511_5512delTT (p.Phe1837LeufsX11) 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 (e.g. c.5712dupA (p.Ser1905fsX25), c.5908C>T (p.Gln1970X), c.6404_6405insTT (p.Arg2136fsX1)). The variant was absent in 250904 control chromosomes (gnomAD). To our knowledge, no occurrence of c.5511_5512delTT in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has provided clinical-significance assessments for this variant in ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV003470674	SCV004212179	likely pathogenic	Familial cancer of breast	2024-03-06	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470674	SCV004931704	pathogenic	Familial cancer of breast	2024-01-25	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Laboratory for Genotyping Development, RIKEN	RCV003159702	SCV002758397	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research