Variant 2-205683363-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003872.3(NRP2):c.73G>A(p.Asp25Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,459,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NRP2
NM_003872.3 missense, splice_region

Scores

Splicing: ADA: 0.9993

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.89

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRP2	NM_003872.3 linkuse as main transcript	c.73G>A	p.Asp25Asn	missense_variant, splice_region_variant	1/17	ENST00000357785.10	NP_003863.2	O60462-3Q7Z3T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10 linkuse as main transcript	c.73G>A	p.Asp25Asn	missense_variant, splice_region_variant	1/17	1	NM_003872.3	ENSP00000350432.5		O60462-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459176

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000118

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NRP2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 29, 2024

The NRP2 c.73G>A variant is predicted to result in the amino acid substitution p.Asp25Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;.;.;.;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.20

T;T;T;T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.075

N;.;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.010

N;N;N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.094

T;T;T;T;T;T;T

Sift4G

Benign

0.50

T;T;T;T;T;T;T

Polyphen

0.023

B;.;.;B;B;B;B

Vest4

0.30

MVP

0.88

MPC

0.81

ClinPred

0.23

GERP RS

5.8

Varity_R

0.17

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over