2-205788239-T-C

Position:

• chr2-205788239-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003872.3(NRP2):​c.2426-3996T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,046 control chromosomes in the GnomAD database, including 5,805 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 0.27 (5805 hom., cov: 31)
• Consequence: NRP2 NM_003872.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP2	NM_003872.3	c.2426-3996T>C		intron_variant		ENST00000357785.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP2	ENST00000357785.10	c.2426-3996T>C		intron_variant		1	NM_003872.3	P3
NRP2	ENST00000360409.7	c.2441-3996T>C		intron_variant		1		A1
NRP2	ENST00000412873.2	c.2426-6515T>C		intron_variant		1
NRP2	ENST00000467850.1	n.276-3996T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41083 AN: 151928 Hom.: 5784 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.271 AC: 41140 AN: 152046 Hom.: 5805 Cov.: 31 AF XY: 0.269 AC XY: 19975 AN XY: 74304

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.309

Alfa AF: 0.271 Hom.: 8005

Bravo AF: 0.271

Asia WGS AF: 0.302 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3755232; hg19: chr2-206652963;