rs6857

Positions:

• chr19-44888997-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042724.2(NECTIN2):​c.*618C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,328 control chromosomes in the GnomAD database, including 1,378 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 0.13 (1367 hom., cov: 30)
  • Exomes 𝑓: 0.12 (11 hom.)
• Consequence: NECTIN2 NM_001042724.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.*618C>T		3_prime_UTR_variant	9/9	ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.*618C>T		3_prime_UTR_variant	9/9	1	NM_001042724.2	ENSP00000252483	P3
	ENST00000585408.1	n.114+1766G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19061 AN: 151368 Hom.: 1358 Cov.: 30

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.120 AC: 101 AN: 842 Hom.: 11 Cov.: 0 AF XY: 0.120 AC XY: 52 AN XY: 432

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0980

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.126 AC: 19099 AN: 151486 Hom.: 1367 Cov.: 30 AF XY: 0.128 AC XY: 9457 AN XY: 74002

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.106

Alfa AF: 0.143 Hom.: 586

Bravo AF: 0.115

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6857; hg19: chr19-45392254;