rs377702

Variant names:

• chr19-44859410-G-A
• rs377702
• NM_001042724.2:c.89-5861G>A

Variant summary

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

The NM_001042724.2(NECTIN2):​c.89-5861G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,032 control chromosomes in the GnomAD database, including 9,385 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 0.34 (9385 hom., cov: 32)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.89-5861G>A		intron	N/A	NP_001036189.1	Q92692-1
	NECTIN2	NM_002856.3		c.89-5861G>A		intron	N/A	NP_002847.1	Q92692-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.89-5861G>A		intron	N/A	ENSP00000252483.4	Q92692-1
	NECTIN2	ENST00000252485.8	TSL:1	c.89-5861G>A		intron	N/A	ENSP00000252485.3	Q92692-2
	NECTIN2	ENST00000883539.1		c.89-2649G>A		intron	N/A	ENSP00000553598.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51096 AN: 151914 Hom.: 9381 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.336 AC: 51127 AN: 152032 Hom.: 9385 Cov.: 32 AF XY: 0.340 AC XY: 25288 AN XY: 74304

African (AFR) AF: 0.262 AC: 10866 AN: 41474

American (AMR) AF: 0.260 AC: 3964 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1295 AN: 3470

East Asian (EAS) AF: 0.114 AC: 588 AN: 5160

South Asian (SAS) AF: 0.185 AC: 890 AN: 4822

European-Finnish (FIN) AF: 0.558 AC: 5897 AN: 10562

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

European-Non Finnish (NFE) AF: 0.389 AC: 26466 AN: 67968

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.369 Hom.: 5751

Bravo AF: 0.310

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.63
PhyloP100		-1.0
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: rs377702; hg19: chr19-45362667;