ENST00000252485.8:c.1093G>T

Variant names:

• chr19-44878273-G-T
• rs201037066
• ENST00000252485.8:c.1093G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000252485.8(NECTIN2):​c.1093G>T​(p.Val365Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V365M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NECTIN2 ENST00000252485.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21353522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1042+3795G>T		intron_variant	Intron 5 of 8	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3	c.1093G>T	p.Val365Leu	missense_variant	Exon 6 of 6		NP_002847.1
NECTIN2	XM_047439169.1	c.1043-280G>T		intron_variant	Intron 5 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252485.8	c.1093G>T	p.Val365Leu	missense_variant	Exon 6 of 6	1		ENSP00000252485.3
NECTIN2	ENST00000252483.10	c.1042+3795G>T		intron_variant	Intron 5 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000591581.1	c.563-280G>T		intron_variant	Intron 3 of 3	2		ENSP00000465587.1
NECTIN2	ENST00000585601.1	c.85-100G>T		intron_variant	Intron 1 of 1	3		ENSP00000465511.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 991804 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 500890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.12
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.85	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.078
Sift	Benign	0.40	T
Sift4G	Benign	0.25	T
Polyphen		0.58	P
Vest4		0.19
MutPred		0.42		Loss of sheet (P = 0.0126);
MVP		0.81
ClinPred		0.46	T
GERP RS		4.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201037066; hg19: chr19-45381530;