NM_001042724.2:c.1196+1234A>G

Variant names:

• chr19-44883598-A-G
• rs166907
• NM_001042724.2:c.1196+1234A>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.1196+1234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,276 control chromosomes in the GnomAD database, including 330 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 0.034 (330 hom., cov: 32)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 1 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]

ENSG00000267282 (HGNC:56209):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1196+1234A>G		intron_variant	Intron 6 of 8	ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1196+1234A>G		intron_variant	Intron 6 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000592018.1	c.26+1234A>G		intron_variant	Intron 1 of 1	3		ENSP00000468305.1
ENSG00000267282	ENST00000585408.2	n.161-1260T>C		intron_variant	Intron 1 of 1	3
ENSG00000267282	ENST00000787383.1	n.156-1260T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5193 AN: 152158 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0192

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

GnomAD4 genome AF: 0.0342 AC: 5201 AN: 152276 Hom.: 330 Cov.: 32 AF XY: 0.0334 AC XY: 2487 AN XY: 74454

African (AFR) AF: 0.115 AC: 4777 AN: 41544

American (AMR) AF: 0.0157 AC: 240 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5186

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4832

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68034

Other (OTH) AF: 0.0190 AC: 40 AN: 2110

Alfa AF: 0.0292 Hom.: 62

Bravo AF: 0.0391

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.43
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs166907; hg19: chr19-45386855;