Variant 19-54970030-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_017852.5(NLRP2):c.15G>A(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,442 control chromosomes in the GnomAD database, including 30,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.14 ( 2008 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28986 hom. )

Consequence

NLRP2
NM_017852.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.28

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 -14 ACMG points.

BP4

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

BP6

Variant 19-54970030-G-A is Benign according to our data. Variant chr19-54970030-G-A is described in ClinVar as [Benign]. Clinvar id is 3055369.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 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.15G>A	p.Ala5Ala	synonymous_variant	2/13	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.15G>A	p.Ala5Ala	synonymous_variant	2/13	1	NM_017852.5	ENSP00000409370.2		Q9NX02-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21686

AN:

151904

Hom.:

2011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0443

Gnomad SAS

AF:

0.0593

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.147

AC:

36836

AN:

251370

Hom.:

3417

AF XY:

0.148

AC XY:

20081

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0384

Gnomad AMR exome

AF:

0.0884

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.0444

Gnomad SAS exome

AF:

0.0695

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.190

AC:

278020

AN:

1461420

Hom.:

28986

Cov.:

AF XY:

0.187

AC XY:

136174

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.0349

Gnomad4 AMR exome

AF:

0.0906

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.0555

Gnomad4 SAS exome

AF:

0.0713

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.143

AC:

21673

AN:

152022

Hom.:

2008

Cov.:

AF XY:

0.142

AC XY:

10562

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0421

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0438

Gnomad4 SAS

AF:

0.0581

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.186

Hom.:

4251

Bravo

AF:

0.130

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

EpiCase

AF:

0.200

EpiControl

AF:

0.198

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NLRP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.98

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over