2-205698534-T-C

Variant names:

• chr2-205698534-T-C
• rs849556
• NM_003872.3:c.251+813T>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.251+813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,972 control chromosomes in the GnomAD database, including 34,474 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 0.66 (34474 hom., cov: 30)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003872.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	NM_003872.3	MANE Select	c.251+813T>C		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.251+813T>C		intron	N/A	NP_957718.1
	NRP2	NM_201279.2		c.251+813T>C		intron	N/A	NP_958436.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	ENST00000357785.10	TSL:1 MANE Select	c.251+813T>C		intron	N/A	ENSP00000350432.5
	NRP2	ENST00000360409.7	TSL:1	c.251+813T>C		intron	N/A	ENSP00000353582.3
	NRP2	ENST00000412873.2	TSL:1	c.251+813T>C		intron	N/A	ENSP00000407626.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100391 AN: 151854 Hom.: 34462 Cov.: 30

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.661 AC: 100435 AN: 151972 Hom.: 34474 Cov.: 30 AF XY: 0.667 AC XY: 49575 AN XY: 74284

African (AFR) AF: 0.470 AC: 19468 AN: 41396

American (AMR) AF: 0.705 AC: 10775 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2501 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4636 AN: 5156

South Asian (SAS) AF: 0.804 AC: 3870 AN: 4816

European-Finnish (FIN) AF: 0.814 AC: 8611 AN: 10584

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48279 AN: 67964

Other (OTH) AF: 0.656 AC: 1381 AN: 2106

Alfa AF: 0.694 Hom.: 112359

Bravo AF: 0.646

Asia WGS AF: 0.825 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		-0.52
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: rs849556; hg19: chr2-206563258;