rs283813

chr19-44885917-T-Achr19-44885917-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042724.2(NECTIN2):c.1197-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 1,545,346 control chromosomes in the GnomAD database, including 9,387 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 0.15 (2850 hom., cov: 32)
  • Exomes 𝑓: 0.084 (6537 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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/exons	MANE	UniProt
NECTIN2	NM_001042724.2	c.1197-20T>A		intron_variant		ENST00000252483.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1197-20T>A		intron_variant		1	NM_001042724.2	P3
	ENST00000585408.1	n.115-3579A>T		intron_variant, non_coding_transcript_variant		3
NECTIN2	ENST00000592018.1	c.28-2193T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23381 AN: 152016 Hom.: 2839 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.112 AC: 28051 AN: 249862 Hom.: 2261 AF XY: 0.104 AC XY: 14117 AN XY: 135386

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0955

Gnomad SAS exome AF: 0.0958

Gnomad FIN exome AF: 0.0536

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0836 AC: 116509 AN: 1393212 Hom.: 6537 Cov.: 30 AF XY: 0.0825 AC XY: 57431 AN XY: 696262

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.0886

Gnomad4 SAS exome AF: 0.0930

Gnomad4 FIN exome AF: 0.0562

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0990

GnomAD4 genome AF: 0.154 AC: 23432 AN: 152134 Hom.: 2850 Cov.: 32 AF XY: 0.153 AC XY: 11413 AN XY: 74366

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0952

Gnomad4 EAS AF: 0.0982

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.138

Alfa AF: 0.118 Hom.: 294

Bravo AF: 0.169

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.3
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs283813; hg19: chr19-45389174; COSMIC: COSV52979398; COSMIC: COSV52979398;