Genetic Variant ENST00000252485.8:c.1172_1174delGGA (chr19-44878340-TGAG-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The ENST00000252485.8(NECTIN2):c.1172_1174delGGA(p.Arg391del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,524,126 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

NECTIN2
ENST00000252485.8 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN2	NM_001042724.2 link	c.1043-3859_1043-3857delGGA		intron_variant	Intron 5 of 8	ENST00000252483.10	NP_001036189.1	Q92692-1
NECTIN2	NM_002856.3 link	c.1172_1174delGGA	p.Arg391del	disruptive_inframe_deletion	Exon 6 of 6		NP_002847.1	Q92692-2
NECTIN2	XM_047439169.1 link	c.1043-201_1043-199delGGA		intron_variant	Intron 5 of 5		XP_047295125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NECTIN2	ENST00000252485.8 link	c.1172_1174delGGA	p.Arg391del	disruptive_inframe_deletion	Exon 6 of 6	1		ENSP00000252485.3	Q92692-2
NECTIN2	ENST00000252483.10 link	c.1043-3859_1043-3857delGGA		intron_variant	Intron 5 of 8	1	NM_001042724.2	ENSP00000252483.4	Q92692-1
NECTIN2	ENST00000591581.1 link	c.563-201_563-199delGGA		intron_variant	Intron 3 of 3	2		ENSP00000465587.1	K7EKE8
NECTIN2	ENST00000585601.1 link	c.85-21_85-19delGGA		intron_variant	Intron 1 of 1	3		ENSP00000465511.1	K7EK87

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000160

AC:

220

AN:

1374698

Hom.:

AF XY:

0.000171

AC XY:

116

AN XY:

678544

show subpopulations

Gnomad4 AFR exome

AF:

0.0000967

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.0000809

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.0000616

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149428

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72878

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00294

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over