rs16837637

Variant names:

• chr2-205766530-A-G
• rs16837637
• NM_003872.3:c.2405-253A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003872.3. 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
	NRP2	NM_003872.3	MANE Select	c.2405-253A>G		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.2405-253A>G		intron	N/A	NP_957718.1
	NRP2	NM_201279.2		c.2405-253A>G		intron	N/A	NP_958436.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	ENST00000357785.10	TSL:1 MANE Select	c.2405-253A>G		intron	N/A	ENSP00000350432.5
	NRP2	ENST00000360409.7	TSL:1	c.2405-253A>G		intron	N/A	ENSP00000353582.3
	NRP2	ENST00000412873.2	TSL:1	c.2405-253A>G		intron	N/A	ENSP00000407626.2

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

African (AFR) AF: 0.299 AC: 12388 AN: 41440

American (AMR) AF: 0.629 AC: 9600 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3271 AN: 5152

South Asian (SAS) AF: 0.483 AC: 2325 AN: 4814

European-Finnish (FIN) AF: 0.533 AC: 5614 AN: 10542

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42514 AN: 67954

Other (OTH) AF: 0.547 AC: 1150 AN: 2102

Alfa AF: 0.598 Hom.: 60744

Bravo AF: 0.524

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.56
PhyloP100		0.31
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: rs16837637; hg19: chr2-206631254;