Variant rs2217659 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017852.5(NLRP2):c.312G>A(p.Lys104Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,601,674 control chromosomes in the GnomAD database, including 24,770 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2119 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22651 hom. )

Consequence

NLRP2
NM_017852.5 synonymous

Scores

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]

NLRP2 links:

NLRP2 (HGNC:):

NLRP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=0.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP2	NM_017852.5 linkuse as main transcript	c.312G>A	p.Lys104Lys	synonymous_variant	3/13	ENST00000448584.7	NP_060322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP2	ENST00000448584.7 linkuse as main transcript	c.312G>A	p.Lys104Lys	synonymous_variant	3/13	1	NM_017852.5	ENSP00000409370.2		Q9NX02-1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23862

AN:

151952

Hom.:

2122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.181

AC:

45439

AN:

251228

Hom.:

4746

AF XY:

0.176

AC XY:

23871

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.169

AC:

244682

AN:

1449604

Hom.:

22651

Cov.:

AF XY:

0.168

AC XY:

121448

AN XY:

721834

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.157

AC:

23862

AN:

152070

Hom.:

2119

Cov.:

AF XY:

0.156

AC XY:

11604

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.165

Hom.:

1394

Bravo

AF:

0.160

Asia WGS

AF:

0.208

AC:

725

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.73

DANN

Benign

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over