rs1057519879
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePM2
The NM_004048.4(B2M):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
B2M
NM_004048.4 start_lost
NM_004048.4 start_lost
Scores
4
6
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.61
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_004048.4 (B2M) was described as [Likely_pathogenic] in ClinVar as 376368
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
B2M | NM_004048.4 | c.2T>A | p.Met1? | start_lost | 1/4 | ENST00000648006.3 | |
B2M | XM_005254549.4 | c.2T>A | p.Met1? | start_lost | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B2M | ENST00000648006.3 | c.2T>A | p.Met1? | start_lost | 1/4 | NM_004048.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D;D;D;.
REVEL
Uncertain
Sift
Pathogenic
D;D;D;.
Sift4G
Pathogenic
D;D;D;.
Polyphen
D;D;D;D
Vest4
MutPred
Loss of stability (P = 0.0181);Loss of stability (P = 0.0181);Loss of stability (P = 0.0181);Loss of stability (P = 0.0181);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.