rs283814

Positions:

• chr19-44885967-G-A
• chr19-44885967-G-C
• chr19-44885967-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001042724.2(NECTIN2):​c.1227G>A​(p.Pro409Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,602,636 control chromosomes in the GnomAD database, including 4,014 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (277 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3737 hom.)
• Consequence: NECTIN2 NM_001042724.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53

Genes affected

NECTIN2 (HGNC:9707): (nectin cell adhesion molecule 2) This gene encodes a single-pass type I membrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain. This protein is one of the plasma membrane components of adherens junctions. It also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus, and it is involved in cell to cell spreading of these viruses. Variations in this gene have been associated with differences in the severity of multiple sclerosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ENSG00000267282 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-3.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1227G>A	p.Pro409Pro	synonymous_variant	7/9	ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1227G>A	p.Pro409Pro	synonymous_variant	7/9	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000592018.1	c.27-2143G>A		intron_variant		3		ENSP00000468305.1
ENSG00000267282	ENST00000585408.1	n.115-3629C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7786 AN: 152100 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.0676 AC: 98033 AN: 1450418 Hom.: 3737 Cov.: 32 AF XY: 0.0664 AC XY: 47973 AN XY: 722242

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.0464

Gnomad4 ASJ exome AF: 0.0388

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0289

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0773

Gnomad4 OTH exome AF: 0.0672

GnomAD4 genome AF: 0.0512 AC: 7787 AN: 152218 Hom.: 277 Cov.: 32 AF XY: 0.0495 AC XY: 3687 AN XY: 74416

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0270

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0689 Hom.: 446

Bravo AF: 0.0505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.098

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs283814; hg19: chr19-45389224;