rs7254892

Positions:

• chr19-44886339-G-A
• chr19-44886339-G-C

Variant summary

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

The NM_001042724.2(NECTIN2):​c.1347+120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 781,942 control chromosomes in the GnomAD database, including 1,039 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 0.063 (482 hom., cov: 32)
  • Exomes 𝑓: 0.037 (557 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1347+120G>A		intron_variant		ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1347+120G>A		intron_variant		1	NM_001042724.2	ENSP00000252483	P3
	ENST00000585408.1	n.115-4001C>T		intron_variant, non_coding_transcript_variant		3
NECTIN2	ENST00000592018.1	c.28-1771G>A		intron_variant		3		ENSP00000468305

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9515 AN: 152136 Hom.: 482 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0622

GnomAD4 exome AF: 0.0374 AC: 23552 AN: 629688 Hom.: 557 AF XY: 0.0374 AC XY: 12159 AN XY: 325498

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.0238

Gnomad4 ASJ exome AF: 0.0599

Gnomad4 EAS exome AF: 0.0551

Gnomad4 SAS exome AF: 0.0414

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0407

GnomAD4 genome AF: 0.0625 AC: 9519 AN: 152254 Hom.: 482 Cov.: 32 AF XY: 0.0616 AC XY: 4588 AN XY: 74452

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.0708

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0401 Hom.: 122

Bravo AF: 0.0659

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7254892; hg19: chr19-45389596;