X-153884253-G-GC

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 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 id is 804114.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L1CAM	NM_001278116.2	c.-109+1811dupG		intron_variant	Intron 1 of 28	ENST00000370060.7	NP_001265045.1
L1CAM-AS1	NR_130768.1	n.540dupC		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L1CAM	ENST00000370060.7	c.-109+1811dupG		intron_variant	Intron 1 of 28	5	NM_001278116.2	ENSP00000359077.1
ENSG00000284987	ENST00000646191.1	n.97-8310dupG		intron_variant	Intron 1 of 4			ENSP00000493873.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD3 exomes AF: 1.00 AC: 158827 AN: 158842 Hom.: 54270 AF XY: 1.00 AC XY: 50275 AN XY: 50278

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 SAS exome AF: 1.00

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked hydrocephalus syndrome Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs77883713; hg19: chrX-153149708;