rs3771021

Variant names:

• chr2-205745264-G-A
• rs3771021
• NM_003872.3:c.1642-482G>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.1642-482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,098 control chromosomes in the GnomAD database, including 11,299 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 (11299 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.1642-482G>A		intron_variant	Intron 9 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.1642-482G>A		intron_variant	Intron 9 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55597 AN: 151980 Hom.: 11301 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.366 AC: 55598 AN: 152098 Hom.: 11299 Cov.: 32 AF XY: 0.362 AC XY: 26941 AN XY: 74372

African (AFR) AF: 0.181 AC: 7515 AN: 41476

American (AMR) AF: 0.462 AC: 7063 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3472

East Asian (EAS) AF: 0.316 AC: 1639 AN: 5180

South Asian (SAS) AF: 0.315 AC: 1516 AN: 4816

European-Finnish (FIN) AF: 0.361 AC: 3824 AN: 10584

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31040 AN: 67970

Other (OTH) AF: 0.403 AC: 850 AN: 2110

Alfa AF: 0.428 Hom.: 27492

Bravo AF: 0.363

Asia WGS AF: 0.312 AC: 1084 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	4.2
DANN	Benign	0.40
PhyloP100		0.22
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: rs3771021; hg19: chr2-206609988;