2-205697607-C-G

Variant names:

• chr2-205697607-C-G
• NM_003872.3:c.137C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003872.3(NRP2):​c.137C>G​(p.Pro46Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. P46P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NRP2 NM_003872.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.17
• Publications: 0 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]

ENSG00000294037 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

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.137C>G	p.Pro46Arg	missense	Exon 2 of 17	NP_003863.2
	NRP2	NM_201266.2		c.137C>G	p.Pro46Arg	missense	Exon 2 of 17	NP_957718.1	O60462-1
	NRP2	NM_201279.2		c.137C>G	p.Pro46Arg	missense	Exon 2 of 16	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.137C>G	p.Pro46Arg	missense	Exon 2 of 17	ENSP00000350432.5	O60462-3
	NRP2	ENST00000360409.7	TSL:1	c.137C>G	p.Pro46Arg	missense	Exon 2 of 17	ENSP00000353582.3	O60462-1
	NRP2	ENST00000412873.2	TSL:1	c.137C>G	p.Pro46Arg	missense	Exon 2 of 16	ENSP00000407626.2	O60462-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	NRP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		6.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.78		Loss of loop (P = 0.1242)
MVP		0.93
MPC		2.0
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.91
gMVP		0.95
Mutation Taster		=11/89	disease causing

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

hg19: chr2-206562331;