chr2-205695889-G-A

Variant names:

• chr2-205695889-G-A
• rs950219
• NM_003872.3:c.74-1655G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003872.3(NRP2):​c.74-1655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,904 control chromosomes in the GnomAD database, including 8,255 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 0.32 (8255 hom., cov: 31)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 3 publications found

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]

ENSG00000294037 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.74-1655G>A		intron_variant	Intron 1 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.74-1655G>A		intron_variant	Intron 1 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48627 AN: 151786 Hom.: 8234 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.320 AC: 48680 AN: 151904 Hom.: 8255 Cov.: 31 AF XY: 0.314 AC XY: 23287 AN XY: 74240

African (AFR) AF: 0.388 AC: 16059 AN: 41394

American (AMR) AF: 0.307 AC: 4691 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1000 AN: 3466

East Asian (EAS) AF: 0.0469 AC: 242 AN: 5156

South Asian (SAS) AF: 0.147 AC: 705 AN: 4792

European-Finnish (FIN) AF: 0.237 AC: 2509 AN: 10578

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22366 AN: 67956

Other (OTH) AF: 0.331 AC: 693 AN: 2096

Alfa AF: 0.325 Hom.: 22672

Bravo AF: 0.331

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.30
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs950219; hg19: chr2-206560613;