19-54974531-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017852.5(NLRP2):​c.312G>C​(p.Lys104Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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

NLRP2
NM_017852.5 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.100
Variant links:
Genes affected
NLRP2 (HGNC:22948): (NLR family pyrin domain containing 2) This gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). Members of this gene family are thought to be important regulators of immune responses. This gene product interacts with components of the IkB kinase (IKK) complex, and can regulate both caspase-1 and NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity. The pyrin domain is necessary and sufficient for suppression of NF-kB activity. An allelic variant (rs147585490) has been found that is incapable of blocking the transcriptional activity of NF-kB. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]
RPL36AP50 (HGNC:36372): (ribosomal protein L36a pseudogene 50)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08874011).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLRP2NM_017852.5 linkc.312G>C p.Lys104Asn missense_variant Exon 3 of 13 ENST00000448584.7 NP_060322.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NLRP2ENST00000448584.7 linkc.312G>C p.Lys104Asn missense_variant Exon 3 of 13 1 NM_017852.5 ENSP00000409370.2 Q9NX02-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
6.3
DANN
Benign
0.86
DEOGEN2
Benign
0.013
.;.;T;T;.;.;T;.;T;.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.013
N
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.089
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.90
.;.;.;L;L;L;L;L;.;.;.;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.91
.;.;N;N;N;N;N;N;.;N;N;D
REVEL
Benign
0.11
Sift
Uncertain
0.0040
.;.;D;D;T;T;D;T;.;T;T;D
Sift4G
Uncertain
0.016
D;D;D;D;T;T;D;T;T;T;D;D
Polyphen
0.79, 0.65
.;.;.;P;P;P;P;P;.;.;.;.
Vest4
0.23, 0.24, 0.25, 0.25, 0.29, 0.22
MutPred
0.31
Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);.;.;Loss of loop (P = 0.0073);.;
MVP
0.39
MPC
0.22
ClinPred
0.20
T
GERP RS
-2.6
Varity_R
0.098
gMVP
0.063

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: rs2217659; hg19: chr19-55485899; API