Genetic Variant NRP2:c.*2515C>G (chr2-205797573-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003872.3(NRP2):c.*2515C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,418 control chromosomes in the GnomAD database, including 8,920 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 0.33 ( 8881 hom., cov: 32)

Exomes 𝑓: 0.45 ( 39 hom. )

Consequence

NRP2
NM_003872.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.465

Publications

8 publications found

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:

ENSG00000300670 (HGNC:):

ENSG00000300670 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRP2	NM_003872.3	MANE Select	c.*2515C>G	3_prime_UTR	Exon 17 of 17	NP_003863.2
NRP2	NM_201266.2		c.*2515C>G	3_prime_UTR	Exon 17 of 17	NP_957718.1	O60462-1
NRP2	NM_201279.2		c.*2515C>G	3_prime_UTR	Exon 16 of 16	NP_958436.1	O60462-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRP2	ENST00000357785.10	TSL:1 MANE Select	c.*2515C>G	3_prime_UTR	Exon 17 of 17	ENSP00000350432.5	O60462-3
NRP2	ENST00000360409.7	TSL:1	c.*2515C>G	3_prime_UTR	Exon 17 of 17	ENSP00000353582.3	O60462-1
ENSG00000300670	ENST00000773312.1		n.162-11741G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49893

AN:

151908

Hom.:

8880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.446

AC:

175

AN:

392

Hom.:

Cov.:

AF XY:

0.452

AC XY:

114

AN XY:

252

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.456

AC:

164

AN:

360

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.308

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.328

AC:

49921

AN:

152026

Hom.:

8881

Cov.:

AF XY:

0.333

AC XY:

24704

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.201

AC:

8320

AN:

41482

American (AMR)

AF:

0.284

AC:

4343

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1326

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2232

AN:

5170

South Asian (SAS)

AF:

0.582

AC:

2802

AN:

4816

European-Finnish (FIN)

AF:

0.432

AC:

4547

AN:

10534

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.372

AC:

25307

AN:

67966

Other (OTH)

AF:

0.330

AC:

696

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1676

3352

5027

6703

8379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.343

Hom.:

1233

Bravo

AF:

0.307

Asia WGS

AF:

0.506

AC:

1762

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

(source)

DANN

Benign

0.55

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over