chr2-205780523-G-C

Variant names:

• chr2-205780523-G-C
• rs4675542
• NM_003872.3:c.2426-11712G>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.2426-11712G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,080 control chromosomes in the GnomAD database, including 2,814 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 0.17 (2814 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2426-11712G>C		intron_variant	Intron 15 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2426-11712G>C		intron_variant	Intron 15 of 16	1	NM_003872.3	ENSP00000350432.5
NRP2	ENST00000360409.7	c.2441-11712G>C		intron_variant	Intron 15 of 16	1		ENSP00000353582.3
NRP2	ENST00000412873.2	c.2425+13720G>C		intron_variant	Intron 15 of 15	1		ENSP00000407626.2
NRP2	ENST00000467850.1	n.276-11712G>C		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26110 AN: 151958 Hom.: 2813 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.172 AC: 26111 AN: 152080 Hom.: 2814 Cov.: 32 AF XY: 0.176 AC XY: 13078 AN XY: 74326

African (AFR) AF: 0.0478 AC: 1986 AN: 41518

American (AMR) AF: 0.172 AC: 2623 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3462

East Asian (EAS) AF: 0.232 AC: 1197 AN: 5154

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4812

European-Finnish (FIN) AF: 0.312 AC: 3299 AN: 10574

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14636 AN: 67960

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.191 Hom.: 398

Bravo AF: 0.157

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.74
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4675542; hg19: chr2-206645247;