chr2-205683345-C-T

Variant names:

• chr2-205683345-C-T
• rs145169333
• NM_003872.3:c.55C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003872.3(NRP2):​c.55C>T​(p.Gln19*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NRP2 NM_003872.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	NM_003872.3	MANE Select	c.55C>T	p.Gln19*	stop_gained	Exon 1 of 17	NP_003863.2
	NRP2	NM_201266.2		c.55C>T	p.Gln19*	stop_gained	Exon 1 of 17	NP_957718.1	O60462-1
	NRP2	NM_201279.2		c.55C>T	p.Gln19*	stop_gained	Exon 1 of 16	NP_958436.1	O60462-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRP2	ENST00000357785.10	TSL:1 MANE Select	c.55C>T	p.Gln19*	stop_gained	Exon 1 of 17	ENSP00000350432.5	O60462-3
	NRP2	ENST00000360409.7	TSL:1	c.55C>T	p.Gln19*	stop_gained	Exon 1 of 17	ENSP00000353582.3	O60462-1
	NRP2	ENST00000412873.2	TSL:1	c.55C>T	p.Gln19*	stop_gained	Exon 1 of 16	ENSP00000407626.2	O60462-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461214 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726972

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111430

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Benign	0.077
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.16	N
PhyloP100		0.67
Vest4		0.71
GERP RS		2.9
PromoterAI		-0.13	Neutral
Mutation Taster		=4/196	disease causing (fs/PTC)

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: rs145169333; hg19: chr2-206548069;