rs519825

Variant names:

• chr19-44863522-T-C
• rs519825
• NM_001042724.2:c.89-1749T>C

Variant summary

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

The NM_001042724.2(NECTIN2):​c.89-1749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,080 control chromosomes in the GnomAD database, including 9,276 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 0.33 (9276 hom., cov: 32)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.89-1749T>C		intron_variant	Intron 1 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.89-1749T>C		intron_variant	Intron 1 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.89-1749T>C		intron_variant	Intron 1 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.89-1749T>C		intron_variant	Intron 1 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.89-1749T>C		intron_variant	Intron 1 of 5	1		ENSP00000252485.3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50459 AN: 151962 Hom.: 9272 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.332 AC: 50489 AN: 152080 Hom.: 9276 Cov.: 32 AF XY: 0.336 AC XY: 24982 AN XY: 74336

African (AFR) AF: 0.244 AC: 10119 AN: 41484

American (AMR) AF: 0.259 AC: 3948 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3470

East Asian (EAS) AF: 0.114 AC: 593 AN: 5180

South Asian (SAS) AF: 0.184 AC: 888 AN: 4822

European-Finnish (FIN) AF: 0.561 AC: 5907 AN: 10538

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26559 AN: 68012

Other (OTH) AF: 0.326 AC: 688 AN: 2112

Alfa AF: 0.361 Hom.: 37640

Bravo AF: 0.305

Asia WGS AF: 0.162 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		0.20
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: rs519825; hg19: chr19-45366779;