rs6859

Positions:

• chr19-44878777-A-G
• chr19-44878777-A-T

Variant summary

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

The NM_002856.3(NECTIN2):​c.*157A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,424,266 control chromosomes in the GnomAD database, including 246,099 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 0.58 (26305 hom., cov: 30)
  • Exomes 𝑓: 0.59 (219794 hom.)
• Consequence: NECTIN2 NM_002856.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1043-3434A>G		intron_variant		ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.*157A>G		3_prime_UTR_variant	6/6		NP_002847.1
NECTIN2	XM_047439169.1	c.*157A>G		3_prime_UTR_variant	6/6		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252485.8	c.*157A>G		3_prime_UTR_variant	6/6	1		ENSP00000252485.3
NECTIN2	ENST00000252483.10	c.1043-3434A>G		intron_variant		1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000591581.1	c.*157A>G		3_prime_UTR_variant	4/4	2		ENSP00000465587.1
NECTIN2	ENST00000585601.1	c.*318A>G		3_prime_UTR_variant	2/2	3		ENSP00000465511.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88674 AN: 151568 Hom.: 26297 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.586 AC: 746046 AN: 1272580 Hom.: 219794 Cov.: 41 AF XY: 0.588 AC XY: 362254 AN XY: 615696

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.683

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.577

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.585 AC: 88726 AN: 151686 Hom.: 26305 Cov.: 30 AF XY: 0.585 AC XY: 43371 AN XY: 74090

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.607

Alfa AF: 0.587 Hom.: 54971

Bravo AF: 0.598

Asia WGS AF: 0.654 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs6859; hg19: chr19-45382034;