Submissions for variant NM_000057.4(BLM):c.387_389del (p.Lys130del)

dbSNP: rs587778105

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766767	SCV000571037	uncertain significance	not provided	2016-07-29	criteria provided, single submitter	clinical testing	The c.387_389delGAA variant in the BLM gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.387_389delGAA variant results in an in-frame, 3 base pair deletion and results in the loss of the glutamic acid residue at position 130 in the protein, denoted as p.Lys130del. In-frame deletions frequently impact the resultant protein as missense changes do. The c.387_389delGAA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the Exome Aggregation Consortium reports c.387_389delGAA was observed in 36/16508 (0.2%) alleles from individuals of South Asian ancestry, but no homozygous individuals were reported in this cohort. Therefore, we interpret c.387_389delGAA as a variant of uncertain significance.
Invitae	RCV001085649	SCV001011656	likely benign	Bloom syndrome	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001021327	SCV001182929	likely benign	Hereditary cancer-predisposing syndrome	2021-10-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genetic Services Laboratory, University of Chicago	RCV000478740	SCV002066920	uncertain significance	not specified	2021-02-23	criteria provided, single submitter	clinical testing	DNA sequence analysis of the BLM gene demonstrated a 3 base pair deletion in exon 3, c.387_389del. This in-frame deletion is predicted to result in the deletion of a lysine amino acid residue, p.Lys130del. This in-frame sequence change has been described in gnomAD with a low population frequency of 0.028% (rs587778105). This sequence change does not appear to have been previously described in patients with BLM-related disorders and has also not been described as a known benign sequence change in the BLM gene. The functional significance of this sequence change is not known at present and its contribution to this patient's disease phenotype cannot definitively be determined.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000766767	SCV004222491	likely benign	not provided	2023-03-10	criteria provided, single submitter	clinical testing
ITMI	RCV000478740	SCV000084383	not provided	not specified	2013-09-19	no assertion provided	reference population