2-205763745-C-T

Variant names:

• chr2-205763745-C-T
• rs779250419
• NM_003872.3:c.2116C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003872.3(NRP2):​c.2116C>T​(p.Pro706Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P706T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRP2 NM_003872.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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]

NRP2-AS1 (HGNC:40415):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09785986).

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.2116C>T	p.Pro706Ser	missense	Exon 13 of 17	NP_003863.2
	NRP2	NM_201266.2		c.2116C>T	p.Pro706Ser	missense	Exon 13 of 17	NP_957718.1	O60462-1
	NRP2	NM_201279.2		c.2116C>T	p.Pro706Ser	missense	Exon 13 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.2116C>T	p.Pro706Ser	missense	Exon 13 of 17	ENSP00000350432.5	O60462-3
	NRP2	ENST00000360409.7	TSL:1	c.2116C>T	p.Pro706Ser	missense	Exon 13 of 17	ENSP00000353582.3	O60462-1
	NRP2	ENST00000412873.2	TSL:1	c.2116C>T	p.Pro706Ser	missense	Exon 13 of 16	ENSP00000407626.2	O60462-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.74
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.84	L
PhyloP100		1.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.084
Sift	Benign	0.78	T
Sift4G	Benign	0.72	T
Polyphen		0.20	B
Vest4		0.36
MutPred		0.51		Loss of sheet (P = 0.0817)
MVP		0.38
MPC		0.28
ClinPred		0.081	T
GERP RS		5.0
Varity_R		0.055
gMVP		0.62
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs779250419; hg19: chr2-206628469;