Submissions for variant NM_000057.4(BLM):c.1479_1480del (p.Thr494fs)

dbSNP: rs746244182

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000409376	SCV000749523	pathogenic	Bloom syndrome	2024-12-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr494Profs*9) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant is present in population databases (rs746244182, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 371108). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV001011718	SCV001172073	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-07	criteria provided, single submitter	clinical testing	The c.1479_1480delTA pathogenic mutation, located in coding exon 6 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 1479 to 1480, causing a translational frameshift with a predicted alternate stop codon (p.T494Pfs*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.
DASA	RCV000409376	SCV002107145	pathogenic	Bloom syndrome	2022-03-05	criteria provided, single submitter	clinical testing	The c.1479_1480del;p.(Thr494Profs*9) is a null frameshift variant (NMD) in the BLM gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 371108). PS4_moderate. The variant is present at low allele frequencies population databases (rs746244182 – gnomAD 0.00007991%; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.
Baylor Genetics	RCV000409376	SCV004210871	pathogenic	Bloom syndrome	2023-08-04	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000409376	SCV005689357	pathogenic	Bloom syndrome	2024-11-05	criteria provided, single submitter	clinical testing	The BLM c.1479_1480del (p.Thr494ProfsTer9) change deletes two nucleotides to cause a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation or absence of protein due to nonsense-mediated decay. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. This variant has a maximum subpopulation frequency of 0.002% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). In summary, this variant meets criteria to be classified as pathogenic.
Counsyl	RCV000409376	SCV000486590	likely pathogenic	Bloom syndrome	2016-06-28	no assertion criteria provided	clinical testing	This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact [e-mail].
Natera, Inc.	RCV000409376	SCV001460783	pathogenic	Bloom syndrome	2020-09-16	no assertion criteria provided	clinical testing