rs2217659

Variant names:

• chr19-54974531-G-A
• rs2217659
• NM_017852.5:c.312G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54974531-G-A
• chr19-54974531-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 17 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017852.5. 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
	NLRP2	NM_017852.5	MANE Select	c.312G>A	p.Lys104Lys	synonymous	Exon 3 of 13	NP_060322.1
	NLRP2	NM_001174081.3		c.312G>A	p.Lys104Lys	synonymous	Exon 3 of 13	NP_001167552.1
	NLRP2	NM_001348003.2		c.312G>A	p.Lys104Lys	synonymous	Exon 3 of 13	NP_001334932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP2	ENST00000448584.7	TSL:1 MANE Select	c.312G>A	p.Lys104Lys	synonymous	Exon 3 of 13	ENSP00000409370.2
	NLRP2	ENST00000543010.5	TSL:1	c.312G>A	p.Lys104Lys	synonymous	Exon 3 of 13	ENSP00000445135.1
	NLRP2	ENST00000263437.10	TSL:2	c.312G>A	p.Lys104Lys	synonymous	Exon 3 of 13	ENSP00000263437.6

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23862 AN: 151952 Hom.: 2122 Cov.: 32

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

GnomAD2 exomes AF: 0.181 AC: 45439 AN: 251228 AF XY: 0.176

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 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.: 30 AF XY: 0.168 AC XY: 121448 AN XY: 721834

African (AFR) AF: 0.107 AC: 3550 AN: 33298

American (AMR) AF: 0.213 AC: 9529 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3492 AN: 26088

East Asian (EAS) AF: 0.397 AC: 15692 AN: 39556

South Asian (SAS) AF: 0.133 AC: 11443 AN: 85984

European-Finnish (FIN) AF: 0.149 AC: 7954 AN: 53350

Middle Eastern (MID) AF: 0.182 AC: 1049 AN: 5750

European-Non Finnish (NFE) AF: 0.165 AC: 182076 AN: 1100914

Other (OTH) AF: 0.165 AC: 9897 AN: 60008

GnomAD4 genome AF: 0.157 AC: 23862 AN: 152070 Hom.: 2119 Cov.: 32 AF XY: 0.156 AC XY: 11604 AN XY: 74316

African (AFR) AF: 0.107 AC: 4423 AN: 41502

American (AMR) AF: 0.170 AC: 2590 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1958 AN: 5156

South Asian (SAS) AF: 0.136 AC: 654 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10586

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11789 AN: 67976

Other (OTH) AF: 0.161 AC: 340 AN: 2116

Alfa AF: 0.166 Hom.: 1873

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.50
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2217659; hg19: chr19-55485899; COSMIC: COSV54753330; COSMIC: COSV54753330;