chr2-205731212-G-A

Variant names:

• chr2-205731212-G-A
• rs849523
• NM_003872.3:c.1146+3166G>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.1146+3166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,056 control chromosomes in the GnomAD database, including 6,359 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 0.28 (6359 hom., cov: 33)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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.1146+3166G>A		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.1146+3166G>A		intron	N/A	NP_957718.1
	NRP2	NM_201279.2		c.1146+3166G>A		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.1146+3166G>A		intron	N/A	ENSP00000350432.5
	NRP2	ENST00000360409.7	TSL:1	c.1146+3166G>A		intron	N/A	ENSP00000353582.3
	NRP2	ENST00000412873.2	TSL:1	c.1146+3166G>A		intron	N/A	ENSP00000407626.2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42788 AN: 151938 Hom.: 6349 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.282 AC: 42816 AN: 152056 Hom.: 6359 Cov.: 33 AF XY: 0.283 AC XY: 21005 AN XY: 74312

African (AFR) AF: 0.290 AC: 12044 AN: 41470

American (AMR) AF: 0.277 AC: 4235 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3466

East Asian (EAS) AF: 0.558 AC: 2887 AN: 5176

South Asian (SAS) AF: 0.341 AC: 1640 AN: 4816

European-Finnish (FIN) AF: 0.233 AC: 2453 AN: 10538

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17841 AN: 67978

Other (OTH) AF: 0.293 AC: 620 AN: 2114

Alfa AF: 0.269 Hom.: 19873

Bravo AF: 0.283

Asia WGS AF: 0.427 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.50
PhyloP100		1.2
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: rs849523; hg19: chr2-206595936;