2-205716309-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003872.3(NRP2):c.368A>G(p.Lys123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 1,614,066 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.032 (291 hom., cov: 31)
  • Exomes 𝑓: 0.0037 (317 hom.)
• Consequence: NRP2 NM_003872.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.69

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013363659).
• BP6: Variant 2-205716309-A-G is Benign according to our data. Variant chr2-205716309-A-G is described in ClinVar as [Benign]. Clinvar id is 769578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRP2	NM_003872.3	c.368A>G	p.Lys123Arg	missense_variant	3/17	ENST00000357785.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRP2	ENST00000357785.10	c.368A>G	p.Lys123Arg	missense_variant	3/17	1	NM_003872.3	P3

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4915 AN: 152058 Hom.: 291 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.00369 AC: 5390 AN: 1461890 Hom.: 317 Cov.: 31 AF XY: 0.00327 AC XY: 2377 AN XY: 727246

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000452

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000306

Gnomad4 OTH exome AF: 0.00808

GnomAD4 genome AF: 0.0323 AC: 4920 AN: 152176 Hom.: 291 Cov.: 31 AF XY: 0.0313 AC XY: 2329 AN XY: 74400

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00676 Hom.: 102

Bravo AF: 0.0368

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

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
AlphaMissense	Benign	0.089
BayesDel_noAF	Uncertain	0.080
Cadd	Benign	22
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
MetaRNN	Benign	0.013	T;T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T
Vest4		0.19
gMVP		0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs849541; hg19: chr2-206581033;