2-205777613-G-A

Position:

• chr2-205777613-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018534.4(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 NM_018534.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2425+10810G>A		intron_variant		ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2425+10810G>A		intron_variant		1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52603 AN: 151828 Hom.: 9405 Cov.: 31

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: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.346 AC: 52609 AN: 151946 Hom.: 9402 Cov.: 31 AF XY: 0.344 AC XY: 25542 AN XY: 74262

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.339

Alfa AF: 0.374 Hom.: 21953

Bravo AF: 0.342

Asia WGS AF: 0.248 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs2160328; hg19: chr2-206642337; COSMIC: COSV55934534; COSMIC: COSV55934534;