rs4803766

Positions:

• chr19-44867911-G-A
• chr19-44867911-G-T

Variant summary

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

The NM_001042724.2(NECTIN2):​c.478+2251G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,760 control chromosomes in the GnomAD database, including 15,097 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 0.44 (15097 hom., cov: 30)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.478+2251G>A		intron_variant		ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.478+2251G>A		intron_variant			NP_002847.1
NECTIN2	XM_047439169.1	c.478+2251G>A		intron_variant			XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.478+2251G>A		intron_variant		1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.478+2251G>A		intron_variant		1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66984 AN: 151642 Hom.: 15069 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.442 AC: 67054 AN: 151760 Hom.: 15097 Cov.: 30 AF XY: 0.436 AC XY: 32377 AN XY: 74176

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.458

Alfa AF: 0.441 Hom.: 28549

Bravo AF: 0.461

Asia WGS AF: 0.500 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4803766; hg19: chr19-45371168;