Variant 19-44871907-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001042724.2(NECTIN2):c.533C>T(p.Thr178Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,614,182 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 4 hom. )

Consequence

NECTIN2
NM_001042724.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00100

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051710606).

BP6

Variant 19-44871907-C-T is Benign according to our data. Variant chr19-44871907-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049638.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NECTIN2	NM_001042724.2 linkuse as main transcript	c.533C>T	p.Thr178Met	missense_variant	3/9	ENST00000252483.10
NECTIN2	NM_002856.3 linkuse as main transcript	c.533C>T	p.Thr178Met	missense_variant	3/6
NECTIN2	XM_047439169.1 linkuse as main transcript	c.533C>T	p.Thr178Met	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.533C>T	p.Thr178Met	missense_variant	3/9	1	NM_001042724.2	P3	Q92692-1
NECTIN2	ENST00000252485.8 linkuse as main transcript	c.533C>T	p.Thr178Met	missense_variant	3/6	1		A2	Q92692-2
NECTIN2	ENST00000591581.1 linkuse as main transcript	c.56C>T	p.Thr19Met	missense_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00134

AC:

337

AN:

250834

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00220

AC:

3221

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1554

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00274

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152300

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00147

AC:

178

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00219

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

Mar 10, 2023

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

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.8

DANN

Benign

0.83

DEOGEN2

Benign

0.31

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.60

N;N

REVEL

Benign

0.056

Sift

Benign

0.037

D;T

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.0060

B;B

Vest4

0.13

MVP

0.068

MPC

0.41

ClinPred

0.0077

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.80

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