rs12768

Variant names:

• chr19-55000769-C-A
• rs12768
• NM_017852.5:c.3060C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-55000769-C-A
• chr19-55000769-C-G
• chr19-55000769-C-T

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.3060C>A​(p.Ile1020Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,610,080 control chromosomes in the GnomAD database, including 224,951 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 0.53 (21657 hom., cov: 29)
  • Exomes 𝑓: 0.52 (203294 hom.)
• Consequence: NLRP2 NM_017852.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 29 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-1.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP2	NM_017852.5	c.3060C>A	p.Ile1020Ile	synonymous_variant	Exon 13 of 13	ENST00000448584.7	NP_060322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP2	ENST00000448584.7	c.3060C>A	p.Ile1020Ile	synonymous_variant	Exon 13 of 13	1	NM_017852.5	ENSP00000409370.2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79836 AN: 151518 Hom.: 21622 Cov.: 29

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.558

GnomAD2 exomes AF: 0.565 AC: 141895 AN: 251324 AF XY: 0.557

Gnomad AFR exome AF: 0.461

Gnomad AMR exome AF: 0.755

Gnomad ASJ exome AF: 0.582

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.524 AC: 763702 AN: 1458444 Hom.: 203294 Cov.: 40 AF XY: 0.524 AC XY: 380284 AN XY: 725704

African (AFR) AF: 0.470 AC: 15668 AN: 33358

American (AMR) AF: 0.746 AC: 33357 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 15049 AN: 26108

East Asian (EAS) AF: 0.724 AC: 28745 AN: 39688

South Asian (SAS) AF: 0.542 AC: 46729 AN: 86168

European-Finnish (FIN) AF: 0.476 AC: 25383 AN: 53366

Middle Eastern (MID) AF: 0.588 AC: 3389 AN: 5760

European-Non Finnish (NFE) AF: 0.508 AC: 562862 AN: 1109022

Other (OTH) AF: 0.540 AC: 32520 AN: 60270

GnomAD4 genome AF: 0.527 AC: 79922 AN: 151636 Hom.: 21657 Cov.: 29 AF XY: 0.528 AC XY: 39131 AN XY: 74060

African (AFR) AF: 0.479 AC: 19760 AN: 41292

American (AMR) AF: 0.661 AC: 10064 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2048 AN: 3464

East Asian (EAS) AF: 0.709 AC: 3649 AN: 5150

South Asian (SAS) AF: 0.544 AC: 2606 AN: 4792

European-Finnish (FIN) AF: 0.478 AC: 5027 AN: 10506

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35021 AN: 67906

Other (OTH) AF: 0.560 AC: 1177 AN: 2100

Alfa AF: 0.525 Hom.: 36022

Bravo AF: 0.539

Asia WGS AF: 0.637 AC: 2218 AN: 3478

EpiCase AF: 0.529

EpiControl AF: 0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.090
DANN	Benign	0.43
PhyloP100		-1.6
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: rs12768; hg19: chr19-55512137; COSMIC: COSV107216338;