chr2-205687254-C-T

Variant names:

• chr2-205687254-C-T
• rs861078
• NM_003872.3:c.73+3891C>T

Variant summary

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

The NM_003872.3(NRP2):​c.73+3891C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,060 control chromosomes in the GnomAD database, including 29,174 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 0.60 (29174 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 6 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.73+3891C>T		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.73+3891C>T		intron_variant	Intron 1 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91506 AN: 151942 Hom.: 29157 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.602 AC: 91546 AN: 152060 Hom.: 29174 Cov.: 32 AF XY: 0.609 AC XY: 45291 AN XY: 74314

African (AFR) AF: 0.396 AC: 16430 AN: 41458

American (AMR) AF: 0.655 AC: 10006 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2465 AN: 3466

East Asian (EAS) AF: 0.898 AC: 4639 AN: 5166

South Asian (SAS) AF: 0.824 AC: 3970 AN: 4818

European-Finnish (FIN) AF: 0.690 AC: 7306 AN: 10590

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44612 AN: 67970

Other (OTH) AF: 0.619 AC: 1306 AN: 2110

Alfa AF: 0.644 Hom.: 103228

Bravo AF: 0.588

Asia WGS AF: 0.821 AC: 2856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.22
DANN	Benign	0.84
PhyloP100		-2.4
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: rs861078; hg19: chr2-206551978;