2-205711459-C-A

Variant names:

• chr2-205711459-C-A
• rs863707
• NM_003872.3:c.252-4734C>A

Variant summary

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

The NM_003872.3(NRP2):​c.252-4734C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,994 control chromosomes in the GnomAD database, including 22,565 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 0.49 (22565 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.252-4734C>A		intron_variant	Intron 2 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.252-4734C>A		intron_variant	Intron 2 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75202 AN: 151876 Hom.: 22556 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.495 AC: 75230 AN: 151994 Hom.: 22565 Cov.: 32 AF XY: 0.507 AC XY: 37705 AN XY: 74296

African (AFR) AF: 0.142 AC: 5888 AN: 41438

American (AMR) AF: 0.578 AC: 8842 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4179 AN: 5162

South Asian (SAS) AF: 0.753 AC: 3620 AN: 4808

European-Finnish (FIN) AF: 0.729 AC: 7696 AN: 10564

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41049 AN: 67934

Other (OTH) AF: 0.492 AC: 1041 AN: 2116

Alfa AF: 0.535 Hom.: 2984

Bravo AF: 0.468

Asia WGS AF: 0.716 AC: 2490 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.44
DANN	Benign	0.39
PhyloP100		-1.0
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: rs863707; hg19: chr2-206576183;