VCV000589419.26 - ClinVar

NM_001278116.2(L1CAM):c.649A>C (p.Arg217=)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(8)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001278116.2(L1CAM):c.649A>C (p.Arg217=)

Variation ID: 589419 Accession: VCV000589419.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq28 X: 153870835 (GRCh38) [ NCBI UCSC ] X: 153136290 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 8, 2018	Oct 20, 2024	Jan 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001278116.2:c.649A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001265045.1:p.Arg217=	synonymous
NM_000425.5:c.649A>C	NP_000416.1:p.Arg217=	synonymous
NM_001143963.2:c.634A>C	NP_001137435.1:p.Arg212=	synonymous
NM_024003.3:c.649A>C	NP_076493.1:p.Arg217=	synonymous
NC_000023.11:g.153870835T>G
NC_000023.10:g.153136290T>G
NG_009645.3:g.43389A>C
LRG_14t1:c.649A>C	LRG_14p1:p.Arg217=
LRG_14t2:c.649A>C	LRG_14p2:p.Arg217=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000023.11:153870834:T:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00014

Trans-Omics for Precision Medicine (TOPMed) 0.00019

Exome Aggregation Consortium (ExAC) 0.00021

The Genome Aggregation Database (gnomAD), exomes 0.00025

Links

dbSNP: rs201204893 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
L1CAM		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1266	1531

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Apr 1, 2023	RCV001709685.19
X-linked complicated corpus callosum dysgenesis	Benign (1)	criteria provided, single submitter	Aug 19, 2021	RCV001730710.9
Spastic paraplegia	Likely benign (1)	criteria provided, single submitter	Jan 29, 2024	RCV000865401.15
X-linked hydrocephalus syndrome	Benign (1)	criteria provided, single submitter	Aug 19, 2021	RCV001730708.9
MASA syndrome	Benign (1)	criteria provided, single submitter	Aug 19, 2021	RCV001730709.9
Inborn genetic diseases	Benign (1)	criteria provided, single submitter	Oct 10, 2016	RCV002318830.9

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001937806.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (Aug 19, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	X-linked complicated corpus callosum dysgenesis Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001981198.1 First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021
Benign (Aug 19, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	MASA syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001981199.1 First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021
Benign (Aug 19, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	X-linked hydrocephalus syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001981200.1 First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021
Likely benign (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Spastic paraplegia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001006357.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Benign (Oct 10, 2016)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000850249.5 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (X-linked inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005206890.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Apr 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004167183.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: L1CAM: BP4, BP7, BS2 Number of individuals with the variant: 1

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs201204893 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001278116.2(L1CAM):c.649A>C (p.Arg217=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs201204893 ...