rs398122820
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_004048.4(B2M):c.286G>A(p.Asp96Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
B2M
NM_004048.4 missense
NM_004048.4 missense
Scores
4
11
Clinical Significance
Conservation
PhyloP100: 4.68
Genes affected
B2M (HGNC:914): (beta-2-microglobulin) This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. The encoded antimicrobial protein displays antibacterial activity in amniotic fluid. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.[provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-44715641-G-A is Pathogenic according to our data. Variant chr15-44715641-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 31907.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-44715641-G-A is described in UniProt as null. Variant chr15-44715641-G-A is described in UniProt as null. Variant chr15-44715641-G-A is described in UniProt as null. Variant chr15-44715641-G-A is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3139421). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
B2M | NM_004048.4 | c.286G>A | p.Asp96Asn | missense_variant | 2/4 | ENST00000648006.3 | |
B2M | XM_005254549.4 | c.286G>A | p.Asp96Asn | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B2M | ENST00000648006.3 | c.286G>A | p.Asp96Asn | missense_variant | 2/4 | NM_004048.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Non-Hodgkin lymphoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Familial visceral amyloidosis, Ostertag type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 14, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
REVEL
Benign
Sift4G
Uncertain
D;D;D;.
Polyphen
0.070
.;B;B;B
Vest4
MutPred
0.55
.;Loss of phosphorylation at Y98 (P = 0.0691);Loss of phosphorylation at Y98 (P = 0.0691);Loss of phosphorylation at Y98 (P = 0.0691);
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at