chr2-205763753-C-A

Variant names:

• chr2-205763753-C-A
• NM_003872.3:c.2124C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003872.3(NRP2):​c.2124C>A​(p.His708Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H708H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRP2 NM_003872.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

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]

ENSG00000225216 (HGNC:40415):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16647479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2124C>A	p.His708Gln	missense_variant	Exon 13 of 17	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2124C>A	p.His708Gln	missense_variant	Exon 13 of 17	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.048	T;.;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.0	N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.52	P;B;B;B;B
Vest4		0.21
MutPred		0.49		Gain of disorder (P = 0.0345);Gain of disorder (P = 0.0345);Gain of disorder (P = 0.0345);Gain of disorder (P = 0.0345);Gain of disorder (P = 0.0345);
MVP		0.53
MPC		0.23
ClinPred		0.26	T
GERP RS		5.8
Varity_R		0.083
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-206628477;