Variant chr19-44878362-T-TGGAGGAGCAGGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The ENST00000252485.8(NECTIN2):c.1191_1202dup(p.Gly398_Ala401dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,552,284 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

NECTIN2
ENST00000252485.8 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.54

Variant links:

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]

NECTIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 19-44878362-T-TGGAGGAGCAGGA is Benign according to our data. Variant chr19-44878362-T-TGGAGGAGCAGGA is described in ClinVar as [Likely_benign]. Clinvar id is 3056189.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NECTIN2	NM_001042724.2 linkuse as main transcript	c.1043-3840_1043-3829dup		intron_variant		ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3 linkuse as main transcript	c.1191_1202dup	p.Gly398_Ala401dup	inframe_insertion	6/6		NP_002847.1
NECTIN2	XM_047439169.1 linkuse as main transcript	c.1043-182_1043-171dup		intron_variant			XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252485.8 linkuse as main transcript	c.1191_1202dup	p.Gly398_Ala401dup	inframe_insertion	6/6	1		ENSP00000252485	A2	Q92692-2
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.1043-3840_1043-3829dup		intron_variant		1	NM_001042724.2	ENSP00000252483	P3	Q92692-1
NECTIN2	ENST00000585601.1 linkuse as main transcript	c.85-2_94dup		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000465511
NECTIN2	ENST00000591581.1 linkuse as main transcript	c.565-182_565-171dup		intron_variant		2		ENSP00000465587

Frequencies

GnomAD3 genomes

AF:

0.000323

AC:

AN:

151558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00296

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000698

AC:

110

AN:

157680

Hom.:

AF XY:

0.000446

AC XY:

AN XY:

83040

show subpopulations

Gnomad AFR exome

AF:

0.000110

Gnomad AMR exome

AF:

0.00426

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000112

AC:

157

AN:

1400608

Hom.:

Cov.:

AF XY:

0.0000767

AC XY:

AN XY:

690930

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.00403

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:

0.000206

GnomAD4 genome

AF:

0.000323

AC:

AN:

151676

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NECTIN2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 01, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over