ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7663C>A (p.His2555Asn)

dbSNP: rs786203651
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167054 SCV000217881 uncertain significance Hereditary cancer-predisposing syndrome 2014-11-28 criteria provided, single submitter clinical testing The p.H2555N variant (also known as c.7663C>A), located in coding exon 51 of the ATM gene, results from a C to A substitution at nucleotide position 7663. The histidine at codon 2555 is replaced by asparagine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 22,000 alleles tested) in our clinical cohort. 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 p.H2555N remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003605608 SCV004485103 uncertain significance Ataxia-telangiectasia syndrome 2022-12-23 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2555 of the ATM protein (p.His2555Asn). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 187335).

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