chr2-205770145-G-A

Variant names:

• chr2-205770145-G-A
• rs16837641
• NM_003872.3:c.2425+3342G>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.2425+3342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,034 control chromosomes in the GnomAD database, including 7,488 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 0.30 (7488 hom., cov: 32)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003872.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	NM_003872.3	MANE Select	c.2425+3342G>A		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.2440+3327G>A		intron	N/A	NP_957718.1
	NRP2	NM_201279.2		c.2425+3342G>A		intron	N/A	NP_958436.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	ENST00000357785.10	TSL:1 MANE Select	c.2425+3342G>A		intron	N/A	ENSP00000350432.5
	NRP2	ENST00000360409.7	TSL:1	c.2440+3327G>A		intron	N/A	ENSP00000353582.3
	NRP2	ENST00000412873.2	TSL:1	c.2425+3342G>A		intron	N/A	ENSP00000407626.2

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45314 AN: 151916 Hom.: 7489 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.298 AC: 45321 AN: 152034 Hom.: 7488 Cov.: 32 AF XY: 0.302 AC XY: 22417 AN XY: 74298

African (AFR) AF: 0.179 AC: 7440 AN: 41488

American (AMR) AF: 0.394 AC: 6014 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3472

East Asian (EAS) AF: 0.571 AC: 2936 AN: 5138

South Asian (SAS) AF: 0.348 AC: 1670 AN: 4802

European-Finnish (FIN) AF: 0.252 AC: 2668 AN: 10572

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22461 AN: 67970

Other (OTH) AF: 0.324 AC: 684 AN: 2108

Alfa AF: 0.327 Hom.: 14272

Bravo AF: 0.304

Asia WGS AF: 0.431 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.63
PhyloP100		0.38
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: rs16837641; hg19: chr2-206634869;