Variant 19-44878273-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000252485.8(NECTIN2):c.1093G>A(p.Val365Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,143,934 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. V365V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 30)

Exomes 𝑓: 0.0038 ( 22 hom. )

Consequence

NECTIN2
ENST00000252485.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.48

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008009136).

BP6

Variant 19-44878273-G-A is Benign according to our data. Variant chr19-44878273-G-A is described in ClinVar as [Benign]. Clinvar id is 2650089.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NECTIN2	NM_001042724.2 linkuse as main transcript	c.1042+3795G>A		intron_variant		ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3 linkuse as main transcript	c.1093G>A	p.Val365Met	missense_variant	6/6		NP_002847.1
NECTIN2	XM_047439169.1 linkuse as main transcript	c.1043-280G>A		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.1093G>A	p.Val365Met	missense_variant	6/6	1		ENSP00000252485	A2	Q92692-2
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.1042+3795G>A		intron_variant		1	NM_001042724.2	ENSP00000252483	P3	Q92692-1
NECTIN2	ENST00000585601.1 linkuse as main transcript	c.85-100G>A		intron_variant		3		ENSP00000465511
NECTIN2	ENST00000591581.1 linkuse as main transcript	c.565-280G>A		intron_variant		2		ENSP00000465587

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

426

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.00707

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00424

AC:

536

AN:

126314

Hom.:

AF XY:

0.00539

AC XY:

355

AN XY:

65854

show subpopulations

Gnomad AFR exome

AF:

0.000550

Gnomad AMR exome

AF:

0.000850

Gnomad ASJ exome

AF:

0.00244

Gnomad EAS exome

AF:

0.0000909

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00343

Gnomad OTH exome

AF:

0.00435

GnomAD4 exome

AF:

0.00380

AC:

3773

AN:

991760

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

2074

AN XY:

500868

show subpopulations

Gnomad4 AFR exome

AF:

0.000593

Gnomad4 AMR exome

AF:

0.000611

Gnomad4 ASJ exome

AF:

0.00250

Gnomad4 EAS exome

AF:

0.0000591

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.00848

Gnomad4 NFE exome

AF:

0.00328

Gnomad4 OTH exome

AF:

0.00329

GnomAD4 genome

AF:

0.00280

AC:

426

AN:

152174

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0121

Gnomad4 FIN

AF:

0.00707

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00237

Hom.:

Bravo

AF:

0.00189

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.00294

AC:

ExAC

AF:

0.00257

AC:

143

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

NECTIN2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.60

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Benign

0.054

Sift4G

Benign

0.084

Polyphen

0.86

Vest4

0.22

MVP

0.74

ClinPred

0.012

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

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