2-205697593-C-T

Variant names:

• chr2-205697593-C-T
• rs2228643
• NM_003872.3:c.123C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003872.3(NRP2):​c.123C>T​(p.Thr41Thr) 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:3
• Conservation: PhyloP100: 0.214
• 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]

ENSG00000294037 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.123C>T	p.Thr41Thr	synonymous	Exon 2 of 17	NP_003863.2
	NRP2	NM_201266.2		c.123C>T	p.Thr41Thr	synonymous	Exon 2 of 17	NP_957718.1	O60462-1
	NRP2	NM_201279.2		c.123C>T	p.Thr41Thr	synonymous	Exon 2 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.123C>T	p.Thr41Thr	synonymous	Exon 2 of 17	ENSP00000350432.5	O60462-3
	NRP2	ENST00000360409.7	TSL:1	c.123C>T	p.Thr41Thr	synonymous	Exon 2 of 17	ENSP00000353582.3	O60462-1
	NRP2	ENST00000412873.2	TSL:1	c.123C>T	p.Thr41Thr	synonymous	Exon 2 of 16	ENSP00000407626.2	O60462-2

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

GnomAD2 exomes AF: 0.00541 AC: 1359 AN: 251184 AF XY: 0.00398

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 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

African (AFR) AF: 0.0697 AC: 2334 AN: 33474

American (AMR) AF: 0.00387 AC: 173 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5766

European-Non Finnish (NFE) AF: 0.000265 AC: 295 AN: 1111996

Other (OTH) AF: 0.00488 AC: 295 AN: 60396

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

African (AFR) AF: 0.0701 AC: 2906 AN: 41444

American (AMR) AF: 0.00680 AC: 104 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68004

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00842 Hom.: 27

Bravo AF: 0.0230

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	NRP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2228643; hg19: chr2-206562317;