chr11-119664967-CCCTCCT-C

Variant names:

• chr11-119664967-CCCTCCT-C
• rs137909701
• NM_002855.5:c.1328_1333delAGGAGG

Variant summary

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

The NM_002855.5(NECTIN1):​c.1328_1333delAGGAGG​(p.Glu443_Glu444del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000214 in 1,610,502 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: NECTIN1 NM_002855.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

Genes affected

NECTIN1 (HGNC:9706): (nectin cell adhesion molecule 1) This gene encodes an adhesion protein that plays a role in the organization of adherens junctions and tight junctions in epithelial and endothelial cells. The protein is a calcium(2+)-independent cell-cell adhesion molecule that belongs to the immunoglobulin superfamily and has 3 extracellular immunoglobulin-like loops, a single transmembrane domain (in some isoforms), and a cytoplasmic region. This protein acts as a receptor for glycoprotein D (gD) of herpes simplex viruses 1 and 2 (HSV-1, HSV-2), and pseudorabies virus (PRV) and mediates viral entry into epithelial and neuronal cells. Mutations in this gene cause cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1) as well as non-syndromic cleft lip with or without cleft palate (CL/P). Alternative splicing results in multiple transcript variants encoding proteins with distinct C-termini. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_002855.5	c.1328_1333delAGGAGG	p.Glu443_Glu444del	disruptive_inframe_deletion	Exon 6 of 6	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.1003+10186_1003+10191delAGGAGG		intron_variant	Intron 5 of 7		NP_976030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000264025.8	c.1328_1333delAGGAGG	p.Glu443_Glu444del	disruptive_inframe_deletion	Exon 6 of 6	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000341398.6	n.1003+10186_1003+10191delAGGAGG		intron_variant	Intron 5 of 7	1
NECTIN1	ENST00000531468.2	c.1003+10186_1003+10191delAGGAGG		intron_variant	Intron 5 of 9	3		ENSP00000513010.1

Frequencies

GnomAD3 genomes AF: 0.000277 AC: 42 AN: 151560 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00209

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000395 AC: 91 AN: 230564 Hom.: 0 AF XY: 0.000352 AC XY: 44 AN XY: 124844

Gnomad AFR exome AF: 0.000201

Gnomad AMR exome AF: 0.0000310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000172

Gnomad SAS exome AF: 0.0000357

Gnomad FIN exome AF: 0.00205

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.000208 AC: 303 AN: 1458942 Hom.: 1 AF XY: 0.000200 AC XY: 145 AN XY: 725778

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.0000672

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00235

Gnomad4 NFE exome AF: 0.000125

Gnomad4 OTH exome AF: 0.000365

GnomAD4 genome AF: 0.000277 AC: 42 AN: 151560 Hom.: 1 Cov.: 31 AF XY: 0.000324 AC XY: 24 AN XY: 73978

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00209

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000482

Bravo AF: 0.000204

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 25, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with NECTIN1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.1328_1333del, results in the deletion of 2 amino acid(s) of the NECTIN1 protein (p.Glu443_Glu444del), but otherwise preserves the integrity of the reading frame. -

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: rs137909701; hg19: chr11-119535677;