ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.813_815GAA[2] (p.Lys273del) (rs587779895)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656779 SCV000149233 uncertain significance not provided 2014-01-27 criteria provided, single submitter clinical testing Single pathogenic variants in BLM have only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted BLM c.819_821delGAA at the cDNA level and p.Lys273del at the protein level. The normal sequence, with the bases that are deleted in brackets, is AGAA[delGAA]TTTG. This in frame deletion of three base pairs results in the loss of a single Lysine at a position that is only moderately conserved throughout evolution and is located in the Helicase ATP binding domain (UniProt). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Lys273del was observed with an allele frequency of 0.1% and 0.2% in European and African Americans in the NHLBI Exome Sequencing Project respectively, not frequent enough to be considered a polymorphism. This variant is not predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BLM Lys273del to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants the BLM gene in general, remain unclear.
Invitae RCV000456184 SCV000543341 uncertain significance Bloom syndrome 2019-12-19 criteria provided, single submitter clinical testing This variant, c.819_821delGAA, results in the deletion of 1 amino acid of the BLM protein (p.Lys273del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs780633851, ExAC 0.006%). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 127516). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.
Ambry Genetics RCV000115324 SCV000672936 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-21 criteria provided, single submitter clinical testing Insufficient evidence
Mendelics RCV000456184 SCV000838952 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing

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