2-205728517-T-C

Variant names:

• chr2-205728517-T-C
• rs849525
• NM_003872.3:c.1146+471T>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.1146+471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,126 control chromosomes in the GnomAD database, including 18,544 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 0.45 (18544 hom., cov: 33)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• Publications: 4 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 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.1146+471T>C		intron	N/A	NP_003863.2
	NRP2	NM_201266.2		c.1146+471T>C		intron	N/A	NP_957718.1
	NRP2	NM_201279.2		c.1146+471T>C		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.1146+471T>C		intron	N/A	ENSP00000350432.5
	NRP2	ENST00000360409.7	TSL:1	c.1146+471T>C		intron	N/A	ENSP00000353582.3
	NRP2	ENST00000412873.2	TSL:1	c.1146+471T>C		intron	N/A	ENSP00000407626.2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68785 AN: 152008 Hom.: 18523 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.452 AC: 68826 AN: 152126 Hom.: 18544 Cov.: 33 AF XY: 0.463 AC XY: 34438 AN XY: 74380

African (AFR) AF: 0.150 AC: 6235 AN: 41504

American (AMR) AF: 0.537 AC: 8199 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2160 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4176 AN: 5166

South Asian (SAS) AF: 0.746 AC: 3598 AN: 4826

European-Finnish (FIN) AF: 0.595 AC: 6302 AN: 10590

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36532 AN: 67968

Other (OTH) AF: 0.462 AC: 976 AN: 2114

Alfa AF: 0.418 Hom.: 2075

Bravo AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.0
DANN	Benign	0.37
PhyloP100		0.27
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: rs849525; hg19: chr2-206593241;