chr2-205750342-A-G

Position:

• chr2-205750342-A-G

Variant summary

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

The NM_003872.3(NRP2):​c.1903+501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,000 control chromosomes in the GnomAD database, including 27,408 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 0.59 (27408 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP2	NM_003872.3	c.1903+501A>G		intron_variant		ENST00000357785.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP2	ENST00000357785.10	c.1903+501A>G		intron_variant		1	NM_003872.3	P3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90331 AN: 151880 Hom.: 27412 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.595 AC: 90366 AN: 152000 Hom.: 27408 Cov.: 32 AF XY: 0.590 AC XY: 43836 AN XY: 74292

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.629

Alfa AF: 0.652 Hom.: 42689

Bravo AF: 0.595

Asia WGS AF: 0.492 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0030
DANN	Benign	0.31

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: rs2241155; hg19: chr2-206615066;