2-205766163-C-T

Variant names:

• chr2-205766163-C-T
• rs3771004
• NM_003872.3:c.2404+593C>T

Variant summary

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

The NM_003872.3(NRP2):​c.2404+593C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,058 control chromosomes in the GnomAD database, including 5,313 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 0.26 (5313 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2404+593C>T		intron_variant	Intron 14 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2404+593C>T		intron_variant	Intron 14 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39707 AN: 151940 Hom.: 5312 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.261 AC: 39719 AN: 152058 Hom.: 5313 Cov.: 32 AF XY: 0.259 AC XY: 19279 AN XY: 74318

African (AFR) AF: 0.218 AC: 9062 AN: 41484

American (AMR) AF: 0.256 AC: 3904 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1715 AN: 5144

South Asian (SAS) AF: 0.199 AC: 956 AN: 4816

European-Finnish (FIN) AF: 0.215 AC: 2276 AN: 10584

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19743 AN: 67968

Other (OTH) AF: 0.284 AC: 600 AN: 2116

Alfa AF: 0.277 Hom.: 14415

Bravo AF: 0.262

Asia WGS AF: 0.251 AC: 873 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	0.49
DANN	Benign	0.67
PhyloP100		-0.64
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: rs3771004; hg19: chr2-206630887;