rs1043684

Variant names:

• chr19-55001063-A-G
• rs1043684
• NM_017852.5:c.*165A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017852.5(NLRP2):​c.*165A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 620,660 control chromosomes in the GnomAD database, including 44,935 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 0.37 (10778 hom., cov: 30)
  • Exomes 𝑓: 0.37 (34157 hom.)
• Consequence: NLRP2 NM_017852.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• Publications: 13 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]

NLRP2 Gene-Disease associations (from GenCC):

• oocyte/zygote/embryo maturation arrest 18

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP2	NM_017852.5	MANE Select	c.*165A>G		3_prime_UTR	Exon 13 of 13	NP_060322.1	Q9NX02-1
	NLRP2	NM_001174081.3		c.*165A>G		3_prime_UTR	Exon 13 of 13	NP_001167552.1	Q9NX02-1
	NLRP2	NM_001348003.2		c.*165A>G		3_prime_UTR	Exon 13 of 13	NP_001334932.1	J3KN39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP2	ENST00000448584.7	TSL:1 MANE Select	c.*165A>G		3_prime_UTR	Exon 13 of 13	ENSP00000409370.2	Q9NX02-1
	NLRP2	ENST00000543010.5	TSL:1	c.*165A>G		3_prime_UTR	Exon 13 of 13	ENSP00000445135.1	Q9NX02-1
	NLRP2	ENST00000263437.10	TSL:2	c.*165A>G		3_prime_UTR	Exon 13 of 13	ENSP00000263437.6	J3KN39

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56220 AN: 151700 Hom.: 10780 Cov.: 30

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.375 AC: 175660 AN: 468842 Hom.: 34157 Cov.: 5 AF XY: 0.373 AC XY: 93069 AN XY: 249484

African (AFR) AF: 0.300 AC: 3868 AN: 12896

American (AMR) AF: 0.414 AC: 8843 AN: 21336

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 5475 AN: 14774

East Asian (EAS) AF: 0.200 AC: 6272 AN: 31416

South Asian (SAS) AF: 0.322 AC: 15726 AN: 48844

European-Finnish (FIN) AF: 0.374 AC: 11585 AN: 30954

Middle Eastern (MID) AF: 0.413 AC: 868 AN: 2100

European-Non Finnish (NFE) AF: 0.403 AC: 112938 AN: 279990

Other (OTH) AF: 0.380 AC: 10085 AN: 26532

GnomAD4 genome AF: 0.370 AC: 56240 AN: 151818 Hom.: 10778 Cov.: 30 AF XY: 0.369 AC XY: 27373 AN XY: 74166

African (AFR) AF: 0.301 AC: 12452 AN: 41396

American (AMR) AF: 0.423 AC: 6447 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3470

East Asian (EAS) AF: 0.174 AC: 899 AN: 5156

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4814

European-Finnish (FIN) AF: 0.380 AC: 3994 AN: 10506

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28289 AN: 67944

Other (OTH) AF: 0.390 AC: 820 AN: 2102

Alfa AF: 0.391 Hom.: 8621

Bravo AF: 0.370

Asia WGS AF: 0.276 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.81
DANN	Benign	0.65
PhyloP100		-0.91
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: rs1043684; hg19: chr19-55512431;