NM_001278116.2:c.-109+1811dupG

Variant names:

• chrX-153884253-G-GC
• rs77883713
• NM_001278116.2:c.-109+1811dupG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001278116.2(L1CAM):​c.-109+1811dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: L1CAM NM_001278116.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90
• Publications: 3 publications found

Genes affected

L1CAM (HGNC:6470): (L1 cell adhesion molecule) The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons. [provided by RefSeq, May 2013]

ENSG00000284987 (HGNC:):

L1CAM-AS1 (HGNC:55247): (L1CAM antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-153884253-G-GC is Benign according to our data. Variant chrX-153884253-G-GC is described in ClinVar as Benign. ClinVar VariationId is 804114.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L1CAM	NM_001278116.2	MANE Select	c.-109+1811dupG		intron	N/A	NP_001265045.1	P32004-1
	L1CAM-AS1	NR_130768.1		n.540dupC		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L1CAM	ENST00000370060.7	TSL:5 MANE Select	c.-109+1811dupG		intron	N/A	ENSP00000359077.1	P32004-1
	ENSG00000284987	ENST00000646191.1		n.97-8310dupG		intron	N/A	ENSP00000493873.1	A0A2R8Y4P6
	L1CAM	ENST00000891165.1		c.-109+1811dupG		intron	N/A	ENSP00000561224.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 1.00 AC: 158827 AN: 158842 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 25

Alfa AF: 1.00 Hom.: 6729

Asia WGS AF: 1.00 AC: 2522 AN: 2522

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	X-linked hydrocephalus syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs77883713; hg19: chrX-153149708;