19-44873027-C-G

Variant names:

• chr19-44873027-C-G
• rs519113
• NM_001042724.2:c.775+878C>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.775+878C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,282 control chromosomes in the GnomAD database, including 5,383 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 0.26 (5383 hom., cov: 30)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• Publications: 56 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.775+878C>G		intron_variant	Intron 3 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.775+878C>G		intron_variant	Intron 3 of 5		NP_002847.1
NECTIN2	XM_047439169.1	c.775+878C>G		intron_variant	Intron 3 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.775+878C>G		intron_variant	Intron 3 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000252485.8	c.775+878C>G		intron_variant	Intron 3 of 5	1		ENSP00000252485.3
NECTIN2	ENST00000591581.1	c.295+878C>G		intron_variant	Intron 1 of 3	2		ENSP00000465587.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39342 AN: 151168 Hom.: 5360 Cov.: 30

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.261 AC: 39420 AN: 151282 Hom.: 5383 Cov.: 30 AF XY: 0.256 AC XY: 18905 AN XY: 73860

African (AFR) AF: 0.332 AC: 13632 AN: 41114

American (AMR) AF: 0.304 AC: 4585 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3462

East Asian (EAS) AF: 0.177 AC: 910 AN: 5138

South Asian (SAS) AF: 0.317 AC: 1520 AN: 4802

European-Finnish (FIN) AF: 0.129 AC: 1352 AN: 10492

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15863 AN: 67892

Other (OTH) AF: 0.251 AC: 527 AN: 2096

Alfa AF: 0.218 Hom.: 2166

Bravo AF: 0.272

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.26
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs519113; hg19: chr19-45376284;