15-90749824-TCAA-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000057.4(BLM):βc.557_559delβ(p.Ser186_Lys187delinsTer) variant causes a stop gained, inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 1,587,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. S186S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000057.4 stop_gained, inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.557_559del | p.Ser186_Lys187delinsTer | stop_gained, inframe_deletion | 3/22 | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.557_559del | p.Ser186_Lys187delinsTer | stop_gained, inframe_deletion | 3/22 | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151684Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000487 AC: 7AN: 1436004Hom.: 0 AF XY: 0.00000421 AC XY: 3AN XY: 712930
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151684Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74030
ClinVar
Submissions by phenotype
Bloom syndrome Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 16, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 06, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change creates a premature translational stop signal (p.Ser186*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Bloom syndrome (PMID: 7585968, 17407155). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It is commonly reported in individuals of Japanese ancestry (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 5455). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 17, 1995 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 10, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at