rs283813

Variant names:

• chr19-44885917-T-A
• rs283813
• NM_001042724.2:c.1197-20T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44885917-T-A
• chr19-44885917-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042724.2(NECTIN2):​c.1197-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 1,545,346 control chromosomes in the GnomAD database, including 9,387 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 0.15 (2850 hom., cov: 32)
  • Exomes 𝑓: 0.084 (6537 hom.)
• Consequence: NECTIN2 NM_001042724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 30 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]

ENSG00000267282 (HGNC:56209):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2	c.1197-20T>A		intron_variant	Intron 6 of 8	ENST00000252483.10	NP_001036189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10	c.1197-20T>A		intron_variant	Intron 6 of 8	1	NM_001042724.2	ENSP00000252483.4
NECTIN2	ENST00000592018.1	c.27-2193T>A		intron_variant	Intron 1 of 1	3		ENSP00000468305.1
ENSG00000267282	ENST00000585408.2	n.161-3579A>T		intron_variant	Intron 1 of 1	3
ENSG00000267282	ENST00000787383.1	n.156-3579A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23381 AN: 152016 Hom.: 2839 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.112 AC: 28051 AN: 249862 AF XY: 0.104

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0955

Gnomad FIN exome AF: 0.0536

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0836 AC: 116509 AN: 1393212 Hom.: 6537 Cov.: 30 AF XY: 0.0825 AC XY: 57431 AN XY: 696262

African (AFR) AF: 0.349 AC: 11054 AN: 31690

American (AMR) AF: 0.179 AC: 8001 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2791 AN: 25734

East Asian (EAS) AF: 0.0886 AC: 3483 AN: 39322

South Asian (SAS) AF: 0.0930 AC: 7885 AN: 84770

European-Finnish (FIN) AF: 0.0562 AC: 2999 AN: 53392

Middle Eastern (MID) AF: 0.104 AC: 587 AN: 5644

European-Non Finnish (NFE) AF: 0.0704 AC: 73955 AN: 1049898

Other (OTH) AF: 0.0990 AC: 5754 AN: 58146

GnomAD4 genome AF: 0.154 AC: 23432 AN: 152134 Hom.: 2850 Cov.: 32 AF XY: 0.153 AC XY: 11413 AN XY: 74366

African (AFR) AF: 0.331 AC: 13740 AN: 41456

American (AMR) AF: 0.156 AC: 2390 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 330 AN: 3466

East Asian (EAS) AF: 0.0982 AC: 508 AN: 5172

South Asian (SAS) AF: 0.101 AC: 489 AN: 4824

European-Finnish (FIN) AF: 0.0521 AC: 553 AN: 10616

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5091 AN: 67998

Other (OTH) AF: 0.138 AC: 291 AN: 2108

Alfa AF: 0.118 Hom.: 294

Bravo AF: 0.169

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs283813; hg19: chr19-45389174; COSMIC: COSV52979398; COSMIC: COSV52979398;