Genetic Variant ENST00000272849.7:c.*1087G>A (chr2-205777613-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000272849.7(NRP2):c.*1087G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,946 control chromosomes in the GnomAD database, including 9,402 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 0.35 ( 9402 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NRP2
ENST00000272849.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Publications

6 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000272849.7. 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.2425+10810G>A	intron	N/A	NP_003863.2
NRP2	NM_018534.4		c.*1087G>A	3_prime_UTR	Exon 16 of 16	NP_061004.3
NRP2	NM_201267.2		c.*1087G>A	3_prime_UTR	Exon 16 of 16	NP_957719.1	O60462-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRP2	ENST00000272849.7	TSL:1	c.*1087G>A	3_prime_UTR	Exon 16 of 16	ENSP00000272849.3	O60462-5
NRP2	ENST00000357785.10	TSL:1 MANE Select	c.2425+10810G>A	intron	N/A	ENSP00000350432.5	O60462-3
NRP2	ENST00000360409.7	TSL:1	c.2440+10795G>A	intron	N/A	ENSP00000353582.3	O60462-1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52603

AN:

151828

Hom.:

9405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.338

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.346

AC:

52609

AN:

151946

Hom.:

9402

Cov.:

AF XY:

0.344

AC XY:

25542

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.276

AC:

11429

AN:

41412

American (AMR)

AF:

0.358

AC:

5466

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

951

AN:

3470

East Asian (EAS)

AF:

0.320

AC:

1653

AN:

5162

South Asian (SAS)

AF:

0.213

AC:

1023

AN:

4814

European-Finnish (FIN)

AF:

0.402

AC:

4237

AN:

10552

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26641

AN:

67960

Other (OTH)

AF:

0.339

AC:

713

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1730

3460

5191

6921

8651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.371

Hom.:

45495

Bravo

AF:

0.342

Asia WGS

AF:

0.248

AC:

859

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.4

(source)

DANN

Benign

0.47

PhyloP100

0.065

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over