rs41290128

Variant names:

• chr19-44888248-G-A
• rs41290128
• NM_001042724.2:c.1486G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/19 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
• Publications: 15 publications found

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]

LNCOB1 (HGNC:56209):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042724.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	NM_001042724.2	MANE Select	c.1486G>A	p.Asp496Asn	missense	Exon 9 of 9	NP_001036189.1	Q92692-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN2	ENST00000252483.10	TSL:1 MANE Select	c.1486G>A	p.Asp496Asn	missense	Exon 9 of 9	ENSP00000252483.4	Q92692-1
	NECTIN2	ENST00000883539.1		c.1627G>A	p.Asp543Asn	missense	Exon 10 of 10	ENSP00000553598.1
	NECTIN2	ENST00000883536.1		c.1573G>A	p.Asp525Asn	missense	Exon 10 of 10	ENSP00000553595.1

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

GnomAD2 exomes AF: 0.0298 AC: 7448 AN: 249544 AF XY: 0.0255

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 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

African (AFR) AF: 0.00281 AC: 94 AN: 33478

American (AMR) AF: 0.136 AC: 6081 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0139 AC: 364 AN: 26136

East Asian (EAS) AF: 0.0137 AC: 542 AN: 39700

South Asian (SAS) AF: 0.0223 AC: 1926 AN: 86258

European-Finnish (FIN) AF: 0.00219 AC: 117 AN: 53416

Middle Eastern (MID) AF: 0.0265 AC: 153 AN: 5766

European-Non Finnish (NFE) AF: 0.00846 AC: 9402 AN: 1112000

Other (OTH) AF: 0.0162 AC: 978 AN: 60392

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

African (AFR) AF: 0.00260 AC: 108 AN: 41542

American (AMR) AF: 0.0908 AC: 1386 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5176

South Asian (SAS) AF: 0.0257 AC: 124 AN: 4826

European-Finnish (FIN) AF: 0.00216 AC: 23 AN: 10626

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00812 AC: 552 AN: 68002

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0132 Hom.: 21

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 v4.9

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
PhyloP100		2.1
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
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs41290128; hg19: chr19-45391505; COSMIC: COSV107256657; COSMIC: COSV107256657;