Submissions for variant NM_000051.4(ATM):c.2428A>G (p.Lys810Glu)

gnomAD frequency: 0.00001  dbSNP: rs201909756

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000221054	SCV000275372	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-24	criteria provided, single submitter	clinical testing	The p.K810E variant (also known as c.2428A>G), located in coding exon 15 of the ATM gene, results from an A to G substitution at nucleotide position 2428. The lysine at codon 810 is replaced by glutamic acid, an amino acid with similar properties. This variant has been reported in an individual with colorectal cancer (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231365	SCV000282899	uncertain significance	Ataxia-telangiectasia syndrome	2023-04-28	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 231500). This variant is present in population databases (rs201909756, gnomAD 0.004%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 810 of the ATM protein (p.Lys810Glu).
Color Diagnostics, LLC DBA Color Health	RCV000221054	SCV000687386	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-31	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamic acid at codon 810 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). This variant has been identified in 4/282606 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl	RCV000231365	SCV000799957	uncertain significance	Ataxia-telangiectasia syndrome	2018-05-14	criteria provided, single submitter	clinical testing
GeneDx	RCV002298535	SCV002588012	uncertain significance	not provided	2022-04-26	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Variant has been observed in an individual with colorectal cancer and also in unaffected controls (Yurgelun 2017, Momozawa 2018); This variant is associated with the following publications: (PMID: 28135145, 30287823)
Baylor Genetics	RCV003469033	SCV004212015	uncertain significance	Familial cancer of breast	2023-04-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000231365	SCV002077795	uncertain significance	Ataxia-telangiectasia syndrome	2021-07-19	no assertion criteria provided	clinical testing