11-119664967-C-CCCTCCTCCT

Variant names:

• chr11-119664967-C-CCCTCCTCCT
• rs137909701
• NM_002855.5:c.1325_1333dupAGGAGGAGG

Variant summary

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

The NM_002855.5(NECTIN1):​c.1325_1333dupAGGAGGAGG​(p.Glu442_Glu444dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,610,508 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 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: NECTIN1 NM_002855.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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.1325_1333dupAGGAGGAGG	p.Glu442_Glu444dup	conservative_inframe_insertion	Exon 6 of 6	ENST00000264025.8	NP_002846.3
NECTIN1	NM_203285.2	c.1003+10183_1003+10191dupAGGAGGAGG		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.1325_1333dupAGGAGGAGG	p.Glu442_Glu444dup	conservative_inframe_insertion	Exon 6 of 6	1	NM_002855.5	ENSP00000264025.3
NECTIN1	ENST00000341398.6	n.1003+10183_1003+10191dupAGGAGGAGG		intron_variant	Intron 5 of 7	1
NECTIN1	ENST00000531468.2	c.1003+10183_1003+10191dupAGGAGGAGG		intron_variant	Intron 5 of 9	3		ENSP00000513010.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151560 Hom.: 0 Cov.: 31

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: 0.0000590

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1458948 Hom.: 0 Cov.: 39 AF XY: 0.00000827 AC XY: 6 AN XY: 725784

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151560 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 73978

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: 0.0000590

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;