2-205763651-CTGTTTGGGTT-C

Variant names:

• chr2-205763651-CTGTTTGGGTT-C
• rs2057860786
• NM_003872.3:c.2045-17_2045-8delGGGTTTGTTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_003872.3(NRP2):​c.2045-17_2045-8delGGGTTTGTTT variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRP2 NM_003872.3 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-205763651-CTGTTTGGGTT-C is Benign according to our data. Variant chr2-205763651-CTGTTTGGGTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3353559.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.2045-17_2045-8delGGGTTTGTTT		splice_region_variant, intron_variant	Intron 12 of 16	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.2045-22_2045-13delTGTTTGGGTT		intron_variant	Intron 12 of 16	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NRP2-related disorder Benign:1

Mar 25, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2057860786; hg19: chr2-206628375;