chr2-205758870-C-G

Variant names:

• chr2-205758870-C-G
• rs3771010
• NM_003872.3:c.2045-4804C>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.2045-4804C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,032 control chromosomes in the GnomAD database, including 15,728 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 0.43 (15728 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• 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]

NRP2-AS1 (HGNC:40415):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2045-4804C>G		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.2045-4804C>G		intron_variant	Intron 12 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66016 AN: 151914 Hom.: 15730 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.434 AC: 66022 AN: 152032 Hom.: 15728 Cov.: 32 AF XY: 0.430 AC XY: 31933 AN XY: 74318

African (AFR) AF: 0.246 AC: 10215 AN: 41476

American (AMR) AF: 0.472 AC: 7207 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3470

East Asian (EAS) AF: 0.325 AC: 1677 AN: 5164

South Asian (SAS) AF: 0.243 AC: 1172 AN: 4818

European-Finnish (FIN) AF: 0.473 AC: 4993 AN: 10560

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37119 AN: 67948

Other (OTH) AF: 0.461 AC: 972 AN: 2108

Alfa AF: 0.489 Hom.: 2382

Bravo AF: 0.428

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		0.056
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: rs3771010; hg19: chr2-206623594; COSMIC: COSV55929389; COSMIC: COSV55929389;