Submissions for variant NM_000051.4(ATM):c.4661del (p.Asn1554fs)

dbSNP: rs1064793390

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487368	SCV000565996	pathogenic	not provided	2023-06-07	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000693178	SCV000821035	pathogenic	Ataxia-telangiectasia syndrome	2022-10-24	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: 418723). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn1554Thrfs*9) 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	RCV001525072	SCV001735082	pathogenic	Hereditary cancer-predisposing syndrome	2020-06-23	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 31 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	RCV001525072	SCV002633784	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-14	criteria provided, single submitter	clinical testing	The c.4661delA pathogenic mutation, located in coding exon 30 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 4661, causing a translational frameshift with a predicted alternate stop codon (p.N1554Tfs*9). 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	RCV003470531	SCV004210200	likely pathogenic	Familial cancer of breast	2023-07-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470531	SCV004930338	pathogenic	Familial cancer of breast	2024-01-24	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.