chr19-55001063-A-G

Position:

• chr19-55001063-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP2	NM_017852.5	c.*165A>G		3_prime_UTR_variant	13/13	ENST00000448584.7	NP_060322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP2	ENST00000448584.7	c.*165A>G		3_prime_UTR_variant	13/13	1	NM_017852.5	ENSP00000409370.2

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

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.380

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

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.390

Alfa AF: 0.398 Hom.: 4200

Bravo AF: 0.370

Asia WGS AF: 0.276 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.81
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs1043684; hg19: chr19-55512431;