19-44878777-A-G

Variant names:

• chr19-44878777-A-G
• rs6859
• ENST00000252485.8:c.*157A>G

Variant summary

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

The ENST00000252485.8(NECTIN2):​c.*157A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,424,266 control chromosomes in the GnomAD database, including 246,099 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 0.58 (26305 hom., cov: 30)
  • Exomes 𝑓: 0.59 (219794 hom.)
• Consequence: NECTIN2 ENST00000252485.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 168 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252485.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.1043-3434A>G		intron	N/A	NP_001036189.1
	NECTIN2	NM_002856.3		c.*157A>G		3_prime_UTR	Exon 6 of 6	NP_002847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252485.8	TSL:1	c.*157A>G		3_prime_UTR	Exon 6 of 6	ENSP00000252485.3
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.1043-3434A>G		intron	N/A	ENSP00000252483.4
	NECTIN2	ENST00000591581.1	TSL:2	c.*157A>G		3_prime_UTR	Exon 4 of 4	ENSP00000465587.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88674 AN: 151568 Hom.: 26297 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.586 AC: 746046 AN: 1272580 Hom.: 219794 Cov.: 41 AF XY: 0.588 AC XY: 362254 AN XY: 615696

African (AFR) AF: 0.555 AC: 15576 AN: 28068

American (AMR) AF: 0.729 AC: 13937 AN: 19112

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 11340 AN: 18576

East Asian (EAS) AF: 0.663 AC: 22706 AN: 34254

South Asian (SAS) AF: 0.683 AC: 40859 AN: 59860

European-Finnish (FIN) AF: 0.516 AC: 15415 AN: 29884

Middle Eastern (MID) AF: 0.654 AC: 2580 AN: 3946

European-Non Finnish (NFE) AF: 0.577 AC: 591684 AN: 1026006

Other (OTH) AF: 0.604 AC: 31949 AN: 52874

GnomAD4 genome AF: 0.585 AC: 88726 AN: 151686 Hom.: 26305 Cov.: 30 AF XY: 0.585 AC XY: 43371 AN XY: 74090

African (AFR) AF: 0.554 AC: 22910 AN: 41332

American (AMR) AF: 0.692 AC: 10560 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3468

East Asian (EAS) AF: 0.679 AC: 3467 AN: 5106

South Asian (SAS) AF: 0.690 AC: 3315 AN: 4806

European-Finnish (FIN) AF: 0.513 AC: 5406 AN: 10544

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39023 AN: 67866

Other (OTH) AF: 0.607 AC: 1279 AN: 2108

Alfa AF: 0.585 Hom.: 120625

Bravo AF: 0.598

Asia WGS AF: 0.654 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		-0.41
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: rs6859; hg19: chr19-45382034;