Variant chr19-44878275-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7

The ENST00000252485.8(NECTIN2):c.1095G>T(p.Val365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,151,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

NECTIN2
ENST00000252485.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.852

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 19-44878275-G-T is Benign according to our data. Variant chr19-44878275-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045274.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.852 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NECTIN2	NM_001042724.2 linkuse as main transcript	c.1042+3797G>T		intron_variant		ENST00000252483.10
NECTIN2	NM_002856.3 linkuse as main transcript	c.1095G>T	p.Val365=	synonymous_variant	6/6
NECTIN2	XM_047439169.1 linkuse as main transcript	c.1043-278G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252485.8 linkuse as main transcript	c.1095G>T	p.Val365=	synonymous_variant	6/6	1		A2	Q92692-2
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.1042+3797G>T		intron_variant		1	NM_001042724.2	P3	Q92692-1
NECTIN2	ENST00000585601.1 linkuse as main transcript	c.85-98G>T		intron_variant		3
NECTIN2	ENST00000591581.1 linkuse as main transcript	c.565-278G>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000231

AC:

AN:

125408

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

65250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000454

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000760

Gnomad NFE exome

AF:

0.000588

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000468

AC:

468

AN:

999112

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

245

AN XY:

504340

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.0000307

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000639

Gnomad4 NFE exome

AF:

0.000613

Gnomad4 OTH exome

AF:

0.000360

GnomAD4 genome

AF:

0.000329

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000268

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NECTIN2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2019

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.72

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