chr2-205797573-C-G

Position:

• chr2-205797573-C-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP2	NM_003872.3	c.*2515C>G		3_prime_UTR_variant	17/17	ENST00000357785.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP2	ENST00000357785.10	c.*2515C>G		3_prime_UTR_variant	17/17	1	NM_003872.3	P3
NRP2	ENST00000360409.7	c.*2515C>G		3_prime_UTR_variant	17/17	1		A1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49893 AN: 151908 Hom.: 8880 Cov.: 32

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.: 39 Cov.: 0 AF XY: 0.452 AC XY: 114 AN XY: 252

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.328 AC: 49921 AN: 152026 Hom.: 8881 Cov.: 32 AF XY: 0.333 AC XY: 24704 AN XY: 74280

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.330

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs15994; hg19: chr2-206662297;