2-205762691-T-C

Variant names:

• chr2-205762691-T-C
• rs867344
• NM_003872.3:c.2045-983T>C

Variant summary

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

The NM_003872.3(NRP2):​c.2045-983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,050 control chromosomes in the GnomAD database, including 30,824 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 0.63 (30824 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• 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]

NRP2-AS1 (HGNC:40415):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2045-983T>C		intron_variant	Intron 12 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2045-983T>C		intron_variant	Intron 12 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95840 AN: 151932 Hom.: 30817 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.631 AC: 95891 AN: 152050 Hom.: 30824 Cov.: 32 AF XY: 0.625 AC XY: 46430 AN XY: 74304

African (AFR) AF: 0.543 AC: 22503 AN: 41462

American (AMR) AF: 0.618 AC: 9452 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2561 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2880 AN: 5164

South Asian (SAS) AF: 0.466 AC: 2238 AN: 4800

European-Finnish (FIN) AF: 0.613 AC: 6482 AN: 10574

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.699 AC: 47482 AN: 67972

Other (OTH) AF: 0.660 AC: 1393 AN: 2110

Alfa AF: 0.667 Hom.: 64730

Bravo AF: 0.628

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs867344; hg19: chr2-206627415;