2-205787576-C-G

Variant names:

• chr2-205787576-C-G
• rs10932125
• NM_003872.3:c.2426-4659C>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.2426-4659C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,036 control chromosomes in the GnomAD database, including 13,439 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 0.41 (13439 hom., cov: 33)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 3 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]

ENSG00000300670 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2426-4659C>G		intron_variant	Intron 15 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2426-4659C>G		intron_variant	Intron 15 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62699 AN: 151918 Hom.: 13438 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.413 AC: 62716 AN: 152036 Hom.: 13439 Cov.: 33 AF XY: 0.411 AC XY: 30564 AN XY: 74306

African (AFR) AF: 0.293 AC: 12139 AN: 41458

American (AMR) AF: 0.429 AC: 6551 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1595 AN: 3472

East Asian (EAS) AF: 0.356 AC: 1836 AN: 5162

South Asian (SAS) AF: 0.293 AC: 1411 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5369 AN: 10564

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32309 AN: 67968

Other (OTH) AF: 0.426 AC: 895 AN: 2102

Alfa AF: 0.440 Hom.: 1846

Bravo AF: 0.404

Asia WGS AF: 0.311 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10932125; hg19: chr2-206652300;