rs1023835002
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_004048.4(B2M):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
B2M
NM_004048.4 start_lost
NM_004048.4 start_lost
Scores
5
3
6
Clinical Significance
Conservation
PhyloP100: 2.09
Publications
13 publications found
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]
PATL2 (HGNC:33630): (PAT1 homolog 2) Predicted to enable RNA binding activity. Predicted to be involved in P-body assembly and deadenylation-dependent decapping of nuclear-transcribed mRNA. Predicted to act upstream of or within negative regulation of cytoplasmic mRNA processing body assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
PATL2 Gene-Disease associations (from GenCC):
- oocyte maturation defect 4Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 2 pathogenic variants. Next in-frame start position is after 119 codons. Genomic position: 44716337. Lost 0.986 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004048.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| B2M | NM_004048.4 | MANE Select | c.1A>G | p.Met1? | start_lost | Exon 1 of 4 | NP_004039.1 | ||
| PATL2 | NM_001387263.1 | MANE Select | c.-781T>C | upstream_gene | N/A | NP_001374192.1 | |||
| PATL2 | NM_001387261.1 | c.-603T>C | upstream_gene | N/A | NP_001374190.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| B2M | ENST00000648006.3 | MANE Select | c.1A>G | p.Met1? | start_lost | Exon 1 of 4 | ENSP00000497910.1 | ||
| B2M | ENST00000559916.1 | TSL:1 | c.1A>G | p.Met1? | start_lost | Exon 1 of 3 | ENSP00000453350.1 | ||
| B2M | ENST00000557901.5 | TSL:1 | n.1A>G | non_coding_transcript_exon | Exon 1 of 4 | ENSP00000452861.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00 AC: 0AN: 251244 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
251244
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461546Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727096 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461546
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727096
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53088
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112008
Other (OTH)
AF:
AC:
1
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Other
Revision: