chr19-44869097-T-G

Variant names:

• chr19-44869097-T-G
• rs8104483
• NM_001042724.2:c.479-2756T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042724.2(NECTIN2):​c.479-2756T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,638 control chromosomes in the GnomAD database, including 6,288 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 0.28 (6288 hom., cov: 29)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042724.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.479-2756T>G		intron	N/A	NP_001036189.1
	NECTIN2	NM_002856.3		c.479-2756T>G		intron	N/A	NP_002847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.479-2756T>G		intron	N/A	ENSP00000252483.4
	NECTIN2	ENST00000252485.8	TSL:1	c.479-2756T>G		intron	N/A	ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43049 AN: 151522 Hom.: 6293 Cov.: 29

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.284 AC: 43063 AN: 151638 Hom.: 6288 Cov.: 29 AF XY: 0.285 AC XY: 21079 AN XY: 74090

African (AFR) AF: 0.264 AC: 10881 AN: 41288

American (AMR) AF: 0.404 AC: 6138 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1122 AN: 5146

South Asian (SAS) AF: 0.314 AC: 1502 AN: 4788

European-Finnish (FIN) AF: 0.225 AC: 2370 AN: 10530

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18826 AN: 67904

Other (OTH) AF: 0.305 AC: 642 AN: 2104

Alfa AF: 0.286 Hom.: 17077

Bravo AF: 0.300

Asia WGS AF: 0.278 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8104483; hg19: chr19-45372354;