19-44878362-T-TGGAGGAGCAGGA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000252485.8(NECTIN2):c.1191_1202dup(p.Gly398_Ala401dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,552,284 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: NECTIN2 ENST00000252485.8 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-44878362-T-TGGAGGAGCAGGA is Benign according to our data. Variant chr19-44878362-T-TGGAGGAGCAGGA is described in ClinVar as [Likely_benign]. Clinvar id is 3056189.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECTIN2	NM_001042724.2	c.1043-3840_1043-3829dup		intron_variant		ENST00000252483.10
NECTIN2	NM_002856.3	c.1191_1202dup	p.Gly398_Ala401dup	inframe_insertion	6/6
NECTIN2	XM_047439169.1	c.1043-182_1043-171dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN2	ENST00000252485.8	c.1191_1202dup	p.Gly398_Ala401dup	inframe_insertion	6/6	1		A2
NECTIN2	ENST00000252483.10	c.1043-3840_1043-3829dup		intron_variant		1	NM_001042724.2	P3
NECTIN2	ENST00000585601.1	c.85-2_94dup		splice_polypyrimidine_tract_variant, intron_variant		3
NECTIN2	ENST00000591581.1	c.565-182_565-171dup		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 49 AN: 151558 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00296

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000961

GnomAD3 exomes AF: 0.000698 AC: 110 AN: 157680 Hom.: 0 AF XY: 0.000446 AC XY: 37 AN XY: 83040

Gnomad AFR exome AF: 0.000110

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000112 AC: 157 AN: 1400608 Hom.: 0 Cov.: 32 AF XY: 0.0000767 AC XY: 53 AN XY: 690930

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.00403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000206

GnomAD4 genome AF: 0.000323 AC: 49 AN: 151676 Hom.: 1 Cov.: 30 AF XY: 0.000324 AC XY: 24 AN XY: 74114

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.000169 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NECTIN2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 01, 2020

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs780028480; hg19: chr19-45381619;