19-44869702-C-T

Variant names:

• chr19-44869702-C-T
• rs4803767
• NM_001042724.2:c.479-2151C>T

Variant summary

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

The NM_001042724.2(NECTIN2):​c.479-2151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,332 control chromosomes in the GnomAD database, including 5,012 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 0.25 (5012 hom., cov: 30)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 20 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.479-2151C>T		intron_variant	Intron 2 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.479-2151C>T		intron_variant	Intron 2 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.479-2151C>T		intron_variant	Intron 2 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.479-2151C>T		intron_variant	Intron 2 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.479-2151C>T		intron_variant	Intron 2 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37834 AN: 151218 Hom.: 5015 Cov.: 30

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.250 AC: 37846 AN: 151332 Hom.: 5012 Cov.: 30 AF XY: 0.251 AC XY: 18559 AN XY: 73894

African (AFR) AF: 0.182 AC: 7490 AN: 41234

American (AMR) AF: 0.384 AC: 5814 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3472

East Asian (EAS) AF: 0.218 AC: 1123 AN: 5144

South Asian (SAS) AF: 0.305 AC: 1459 AN: 4784

European-Finnish (FIN) AF: 0.202 AC: 2101 AN: 10398

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17812 AN: 67836

Other (OTH) AF: 0.265 AC: 557 AN: 2100

Alfa AF: 0.253 Hom.: 5107

Bravo AF: 0.264

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		0.21
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: rs4803767; hg19: chr19-45372959;