rs748054605
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000057.4(BLM):c.2696G>A(p.Arg899Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R899G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000057.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.2696G>A | p.Arg899Gln | missense_variant | 14/22 | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.2696G>A | p.Arg899Gln | missense_variant | 14/22 | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152116Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251422Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135888
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727212
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152116Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
Bloom syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 899 of the BLM protein (p.Arg899Gln). This variant is present in population databases (rs748054605, gnomAD 0.007%). 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: 454115). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 05, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 28, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 01, 2023 | The p.R899Q variant (also known as c.2696G>A), located in coding exon 13 of the BLM gene, results from a G to A substitution at nucleotide position 2696. The arginine at codon 899 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at