rs769184675
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000057.4(BLM):c.2407-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
BLM
NM_000057.4 splice_region, splice_polypyrimidine_tract, intron
NM_000057.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.133
Genes affected
BLM (HGNC:1058): (BLM RecQ like helicase) The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 15-90769429-TC-T is Benign according to our data. Variant chr15-90769429-TC-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 454103.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.2407-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.2407-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251312Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135856
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727220
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74362
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Bloom syndrome Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 16, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 10, 2020 | DNA sequence analysis of the BLM gene demonstrated a sequence change in intron 11, c.2407-7del. This change does not appear to have been previously described in patients with BLM-related disorders and has been described in the gnomAD database in eight individuals (dbSNP rs749544427). In silico splice site prediction programs give conflicting results on the effect on splicing of this variant. The functional significance of this sequence change is not known at present and its contribution to a disease phenotype cannot definitively be determined. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at