19-54573906-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130917.3(LILRA2):ā€‹c.28T>Cā€‹(p.Cys10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00015 ( 0 hom., cov: 41)
Exomes š‘“: 0.00012 ( 0 hom. )

Consequence

LILRA2
NM_001130917.3 missense

Scores

3
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00700
Variant links:
Genes affected
LILRA2 (HGNC:6603): (leukocyte immunoglobulin like receptor A2) This gene encodes a member of a family of immunoreceptors that are expressed predominantly on monocytes and B cells, and at lower levels on dendritic cells and natural killer cells. The encoded protein is an activating receptor that inhibits dendritic cell differentiation and antigen presentation and suppresses innate immune response. Alternatively spliced transcript variants encoding different isoforms have been found. This gene is located in a cluster of related genes on chromosome 19 and there is a pseudogene for this gene on chromosome 3. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28244475).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LILRA2NM_001130917.3 linkuse as main transcriptc.28T>C p.Cys10Arg missense_variant 1/8 ENST00000391738.8 NP_001124389.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LILRA2ENST00000391738.8 linkuse as main transcriptc.28T>C p.Cys10Arg missense_variant 1/81 NM_001130917.3 ENSP00000375618 P4Q8N149-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152236
Hom.:
0
Cov.:
41
show subpopulations
Gnomad AFR
AF:
0.000313
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000757
AC:
19
AN:
250980
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135654
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000324
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000120
AC:
175
AN:
1461820
Hom.:
0
Cov.:
158
AF XY:
0.000100
AC XY:
73
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000168
Gnomad4 NFE exome
AF:
0.000143
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152236
Hom.:
0
Cov.:
41
AF XY:
0.000148
AC XY:
11
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 07, 2022The c.28T>C (p.C10R) alteration is located in exon 1 (coding exon 1) of the LILRA2 gene. This alteration results from a T to C substitution at nucleotide position 28, causing the cysteine (C) at amino acid position 10 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.22
T;.;.;.;.;T
Eigen
Benign
-0.070
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.78
T;.;.;.;T;.
M_CAP
Benign
0.00088
T
MetaRNN
Benign
0.28
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PROVEAN
Pathogenic
-9.4
D;D;D;D;D;.
REVEL
Benign
0.081
Sift
Pathogenic
0.0
D;D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;D;.
Vest4
0.61, 0.62, 0.64, 0.43, 0.57
MVP
0.29
MPC
0.12
ClinPred
0.76
D
GERP RS
1.6
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs772749570; hg19: chr19-55085373; COSMIC: COSV52191373; COSMIC: COSV52191373; API