2-205697593-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003872.3(NRP2):c.123C>T(p.Thr41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,613,984 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (101 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (103 hom.)
• Consequence: NRP2 NM_003872.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.214

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 2-205697593-C-T is Benign according to our data. Variant chr2-205697593-C-T is described in ClinVar as [Benign]. Clinvar id is 789973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP2	NM_003872.3	c.123C>T	p.Thr41=	synonymous_variant	2/17	ENST00000357785.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP2	ENST00000357785.10	c.123C>T	p.Thr41=	synonymous_variant	2/17	1	NM_003872.3	P3

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3060 AN: 152006 Hom.: 101 Cov.: 31

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00541 AC: 1359 AN: 251184 Hom.: 48 AF XY: 0.00398 AC XY: 541 AN XY: 135826

Gnomad AFR exome AF: 0.0724

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00215 AC: 3138 AN: 1461860 Hom.: 103 Cov.: 32 AF XY: 0.00187 AC XY: 1358 AN XY: 727236

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00488

GnomAD4 genome AF: 0.0201 AC: 3065 AN: 152124 Hom.: 101 Cov.: 31 AF XY: 0.0193 AC XY: 1439 AN XY: 74374

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00882 Hom.: 22

Bravo AF: 0.0230

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

NRP2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 22, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	10
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2228643; hg19: chr2-206562317;