2-205747861-T-C

Variant names:

• chr2-205747861-T-C
• rs1996412
• NM_003872.3:c.1787-1864T>C

Variant summary

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

The NM_003872.3(NRP2):​c.1787-1864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,966 control chromosomes in the GnomAD database, including 13,205 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 0.38 (13205 hom., cov: 31)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.1787-1864T>C		intron_variant	Intron 10 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.1787-1864T>C		intron_variant	Intron 10 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57339 AN: 151848 Hom.: 13214 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.377 AC: 57324 AN: 151966 Hom.: 13205 Cov.: 31 AF XY: 0.377 AC XY: 27958 AN XY: 74238

African (AFR) AF: 0.102 AC: 4232 AN: 41490

American (AMR) AF: 0.414 AC: 6324 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2601 AN: 5170

South Asian (SAS) AF: 0.336 AC: 1613 AN: 4794

European-Finnish (FIN) AF: 0.461 AC: 4856 AN: 10540

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34636 AN: 67928

Other (OTH) AF: 0.416 AC: 878 AN: 2110

Alfa AF: 0.465 Hom.: 29220

Bravo AF: 0.364

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.3
DANN	Benign	0.63
PhyloP100		1.2
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: rs1996412; hg19: chr2-206612585;