rs16837637

chr2-205766530-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003872.3(NRP2):c.2405-253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,938 control chromosomes in the GnomAD database, including 22,531 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 0.52 (22531 hom., cov: 31)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

Genes affected

NRP2 (HGNC:8005): (neuropilin 2) This gene encodes a member of the neuropilin family of receptor proteins. The encoded transmembrane protein binds to SEMA3C protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C} and SEMA3F protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F}, and interacts with vascular endothelial growth factor (VEGF). This protein may play a role in cardiovascular development, axon guidance, and tumorigenesis. This protein has also been determined to act as a co-receptor for SARS-CoV-2 (which causes COVID-19) to infect host cells. [provided by RefSeq, Jul 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP2	NM_003872.3	c.2405-253A>G		intron_variant		ENST00000357785.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP2	ENST00000357785.10	c.2405-253A>G		intron_variant		1	NM_003872.3	P3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79683 AN: 151818 Hom.: 22519 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.525 AC: 79707 AN: 151938 Hom.: 22531 Cov.: 31 AF XY: 0.523 AC XY: 38818 AN XY: 74256

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.547

Alfa AF: 0.604 Hom.: 41513

Bravo AF: 0.524

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.56

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: rs16837637; hg19: chr2-206631254;