rs41290128

chr19-44888248-G-A

Variant summary

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

The NM_001042724.2(NECTIN2):c.1486G>A(p.Asp496Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,614,100 control chromosomes in the GnomAD database, including 636 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (79 hom., cov: 32)
  • Exomes 𝑓: 0.013 (557 hom.)
• Consequence: NECTIN2 NM_001042724.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

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 (MetaRNN=0.001536727).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECTIN2	NM_001042724.2	c.1486G>A	p.Asp496Asn	missense_variant	9/9	ENST00000252483.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1486G>A	p.Asp496Asn	missense_variant	9/9	1	NM_001042724.2	P3
	ENST00000585408.1	n.114+2515C>T		intron_variant, non_coding_transcript_variant		3
NECTIN2	ENST00000592018.1	c.*3G>A		3_prime_UTR_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2382 AN: 152116 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00812

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0298 AC: 7448 AN: 249544 Hom.: 421 AF XY: 0.0255 AC XY: 3456 AN XY: 135404

Gnomad AFR exome AF: 0.00220

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.0191

Gnomad SAS exome AF: 0.0239

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.00901

Gnomad OTH exome AF: 0.0254

GnomAD4 exome AF: 0.0134 AC: 19657 AN: 1461866 Hom.: 557 Cov.: 31 AF XY: 0.0130 AC XY: 9488 AN XY: 727232

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.0139

Gnomad4 EAS exome AF: 0.0137

Gnomad4 SAS exome AF: 0.0223

Gnomad4 FIN exome AF: 0.00219

Gnomad4 NFE exome AF: 0.00846

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0156 AC: 2381 AN: 152234 Hom.: 79 Cov.: 32 AF XY: 0.0174 AC XY: 1294 AN XY: 74446

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.00216

Gnomad4 NFE AF: 0.00812

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0111 Hom.: 9

Bravo AF: 0.0225

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00283 AC: 11

ESP6500EA AF: 0.00800 AC: 66

ExAC AF: 0.0248 AC: 3000

Asia WGS AF: 0.0380 AC: 133 AN: 3476

EpiCase AF: 0.0111

EpiControl AF: 0.0101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.10	T
Polyphen		0.88	P
Vest4		0.053
MPC		0.38
ClinPred		0.020	T
GERP RS		4.1
Varity_R		0.076
gMVP		0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41290128; hg19: chr19-45391505;