19-44865167-C-T

Position:

• chr19-44865167-C-T

Variant summary

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

The NM_001042724.2(NECTIN2):​c.89-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,265,088 control chromosomes in the GnomAD database, including 185,777 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 0.48 (18858 hom., cov: 31)
  • Exomes 𝑓: 0.54 (166919 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECTIN2	NM_001042724.2	c.89-104C>T		intron_variant		ENST00000252483.10
NECTIN2	NM_002856.3	c.89-104C>T		intron_variant
NECTIN2	XM_047439169.1	c.89-104C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252483.10	c.89-104C>T		intron_variant		1	NM_001042724.2	P3
NECTIN2	ENST00000252485.8	c.89-104C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73199 AN: 151886 Hom.: 18856 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.543 AC: 604699 AN: 1113084 Hom.: 166919 AF XY: 0.542 AC XY: 298341 AN XY: 550716

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.557

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.482 AC: 73216 AN: 152004 Hom.: 18858 Cov.: 31 AF XY: 0.489 AC XY: 36309 AN XY: 74294

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.485

Alfa AF: 0.527 Hom.: 11099

Bravo AF: 0.453

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs394221; hg19: chr19-45368424; COSMIC: COSV52975561;