chr2-205691080-C-A

Variant names:

• chr2-205691080-C-A
• rs849530
• NM_003872.3:c.74-6464C>A

Variant summary

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

The NM_201266.2(NRP2):​c.74-6464C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,966 control chromosomes in the GnomAD database, including 20,654 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 0.51 (20654 hom., cov: 32)
• Consequence: NRP2 NM_201266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201266.2. 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.74-6464C>A		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.74-6464C>A		intron	N/A	NP_957718.1
	NRP2	NM_201279.2		c.74-6464C>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.74-6464C>A		intron	N/A	ENSP00000350432.5
	NRP2	ENST00000360409.7	TSL:1	c.74-6464C>A		intron	N/A	ENSP00000353582.3
	NRP2	ENST00000412873.2	TSL:1	c.74-6464C>A		intron	N/A	ENSP00000407626.2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77676 AN: 151848 Hom.: 20639 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.511 AC: 77727 AN: 151966 Hom.: 20654 Cov.: 32 AF XY: 0.519 AC XY: 38575 AN XY: 74256

African (AFR) AF: 0.376 AC: 15585 AN: 41452

American (AMR) AF: 0.515 AC: 7861 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1986 AN: 3460

East Asian (EAS) AF: 0.749 AC: 3866 AN: 5164

South Asian (SAS) AF: 0.685 AC: 3299 AN: 4814

European-Finnish (FIN) AF: 0.641 AC: 6752 AN: 10528

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36688 AN: 67966

Other (OTH) AF: 0.496 AC: 1045 AN: 2108

Alfa AF: 0.533 Hom.: 16656

Bravo AF: 0.493

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.53
PhyloP100		-0.31
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: rs849530; hg19: chr2-206555804;