19-44873997-G-A

Position:

chr19-44873997-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001042724.2(NECTIN2):c.857G>A(p.Arg286His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,848 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 10 hom. )

Consequence

NECTIN2
NM_001042724.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.31

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073524415).

BP6

Variant 19-44873997-G-A is Benign according to our data. Variant chr19-44873997-G-A is described in ClinVar as [Benign]. Clinvar id is 727455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00501 (763/152166) while in subpopulation AFR AF= 0.0171 (709/41514). AF 95% confidence interval is 0.016. There are 8 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NECTIN2	NM_001042724.2 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	4/9	ENST00000252483.10	NP_001036189.1
NECTIN2	NM_002856.3 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	4/6		NP_002847.1
NECTIN2	XM_047439169.1 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	4/6		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	4/9	1	NM_001042724.2	ENSP00000252483	P3	Q92692-1
NECTIN2	ENST00000252485.8 linkuse as main transcript	c.857G>A	p.Arg286His	missense_variant	4/6	1		ENSP00000252485	A2	Q92692-2
NECTIN2	ENST00000591581.1 linkuse as main transcript	c.380G>A	p.Arg127His	missense_variant	2/4	2		ENSP00000465587
NECTIN2	ENST00000587386.1 linkuse as main transcript	n.56G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00500

AC:

760

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00243

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00154

AC:

386

AN:

251202

Hom.:

AF XY:

0.00119

AC XY:

161

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000622

AC:

909

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

406

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000944

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00501

AC:

763

AN:

152166

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00584

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00186

AC:

226

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.068

Sift

Benign

0.39

T;T

Sift4G

Benign

0.094

T;T

Polyphen

0.31

B;B

Vest4

0.29

MVP

0.11

MPC

0.52

ClinPred

0.0074

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.017

gMVP

0.53

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