rs3770991

Variant names:

• chr2-205791015-A-G
• rs3770991
• NM_003872.3:c.2426-1220A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-205791015-A-G
• chr2-205791015-A-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.2426-1220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,250 control chromosomes in the GnomAD database, including 53,262 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 0.83 (53262 hom., cov: 33)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790
• 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]

ENSG00000300670 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.882 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	NM_003872.3	MANE Select	c.2426-1220A>G		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.2441-1220A>G		intron	N/A	NP_957718.1	O60462-1
	NRP2	NM_201279.2		c.2426-3739A>G		intron	N/A	NP_958436.1	O60462-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	ENST00000357785.10	TSL:1 MANE Select	c.2426-1220A>G		intron	N/A	ENSP00000350432.5	O60462-3
	NRP2	ENST00000360409.7	TSL:1	c.2441-1220A>G		intron	N/A	ENSP00000353582.3	O60462-1
	NRP2	ENST00000412873.2	TSL:1	c.2426-3739A>G		intron	N/A	ENSP00000407626.2	O60462-2

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126665 AN: 152132 Hom.: 53234 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.833 AC: 126749 AN: 152250 Hom.: 53262 Cov.: 33 AF XY: 0.834 AC XY: 62096 AN XY: 74458

African (AFR) AF: 0.710 AC: 29468 AN: 41518

American (AMR) AF: 0.821 AC: 12546 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3091 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4074 AN: 5182

South Asian (SAS) AF: 0.901 AC: 4350 AN: 4830

European-Finnish (FIN) AF: 0.943 AC: 10012 AN: 10616

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60383 AN: 68026

Other (OTH) AF: 0.851 AC: 1795 AN: 2110

Alfa AF: 0.868 Hom.: 14244

Bravo AF: 0.818

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3770991; hg19: chr2-206655739;