Variant chr19-44878340-T-TGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2

The ENST00000252485.8(NECTIN2):c.1172_1174dup(p.Arg391dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,534,678 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0037 ( 6 hom. )

Consequence

NECTIN2
ENST00000252485.8 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.91

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 Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000252485.8

BP6

Variant 19-44878340-T-TGAG is Benign according to our data. Variant chr19-44878340-T-TGAG is described in ClinVar as [Likely_benign]. Clinvar id is 3034381.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NECTIN2	NM_001042724.2 linkuse as main transcript	c.1043-3859_1043-3857dup		intron_variant		ENST00000252483.10
NECTIN2	NM_002856.3 linkuse as main transcript	c.1172_1174dup	p.Arg391dup	inframe_insertion	6/6
NECTIN2	XM_047439169.1 linkuse as main transcript	c.1043-201_1043-199dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252485.8 linkuse as main transcript	c.1172_1174dup	p.Arg391dup	inframe_insertion	6/6	1		A2	Q92692-2
NECTIN2	ENST00000252483.10 linkuse as main transcript	c.1043-3859_1043-3857dup		intron_variant		1	NM_001042724.2	P3	Q92692-1
NECTIN2	ENST00000585601.1 linkuse as main transcript	c.85-21_85-19dup		intron_variant		3
NECTIN2	ENST00000591581.1 linkuse as main transcript	c.565-201_565-199dup		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

336

AN:

149436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000767

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00167

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00171

Gnomad FIN

AF:

0.0000977

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.00396

Gnomad OTH

AF:

0.00147

GnomAD3 exomes

AF:

0.00188

AC:

264

AN:

140176

Hom.:

AF XY:

0.00184

AC XY:

135

AN XY:

73464

show subpopulations

Gnomad AFR exome

AF:

0.000857

Gnomad AMR exome

AF:

0.000907

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.000283

Gnomad NFE exome

AF:

0.00391

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00373

AC:

5171

AN:

1385130

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

2523

AN XY:

683746

show subpopulations

Gnomad4 AFR exome

AF:

0.000639

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.0000803

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.000326

Gnomad4 NFE exome

AF:

0.00457

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00225

AC:

336

AN:

149548

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

151

AN XY:

73004

show subpopulations

Gnomad4 AFR

AF:

0.000765

Gnomad4 AMR

AF:

0.00167

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00172

Gnomad4 FIN

AF:

0.0000977

Gnomad4 NFE

AF:

0.00396

Gnomad4 OTH

AF:

0.00145

Bravo

AF:

0.00207

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 26, 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

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