VCV000287985.17 - ClinVar

NM_005045.4(RELN):c.5961G>T (p.Lys1987Asn)

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.

(6)

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.

Conflicting classifications of pathogenicity
Uncertain significance(4); Benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005045.4(RELN):c.5961G>T (p.Lys1987Asn)

Variation ID: 287985 Accession: VCV000287985.17

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.1 7: 103553668 (GRCh38) [ NCBI UCSC ] 7: 103194115 (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	Dec 6, 2016	Oct 8, 2024	Dec 13, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_005045.4:c.5961G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005036.2:p.Lys1987Asn	missense
NM_173054.3:c.5961G>T	NP_774959.1:p.Lys1987Asn	missense
NC_000007.14:g.103553668C>A
NC_000007.13:g.103194115C>A
NG_011877.2:g.440849G>T

... more HGVS ... less HGVS

Protein change

K1987N

Other names

Canonical SPDI

NC_000007.14:103553667:C:A

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.

0.00040 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.00009

Exome Aggregation Consortium (ExAC) 0.00012

1000 Genomes Project 0.00040

Trans-Omics for Precision Medicine (TOPMed) 0.00053

The Genome Aggregation Database (gnomAD) 0.00057

1000 Genomes Project 30x 0.00062

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00085

Links

ClinGen: CA4421072 dbSNP: rs143948239 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.
RELN		No evidence available	No evidence available	GRCh38 GRCh37	2716	3549

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 specified	Uncertain significance (1)	criteria provided, single submitter	Nov 22, 2016	RCV000297158.4
Familial temporal lobe epilepsy 7 Norman-Roberts syndrome	Benign (1)	criteria provided, single submitter	Dec 13, 2023	RCV000653023.8
not provided	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Oct 11, 2023	RCV000726097.10
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Dec 15, 2021	RCV002518008.2
RELN-related disorder	Likely benign (1)	no assertion criteria provided	Jun 16, 2024	RCV004725146.1

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.
Uncertain significance (Nov 22, 2016)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000614874.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jun 13, 2016)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000341957.4 First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RELN Number of individuals with the variant: 1 Sex: mixed
Uncertain significance (Oct 11, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001814502.4 First in ClinVar: Sep 08, 2021 Last updated: Nov 25, 2023	Comment: In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35668055)
Benign (Dec 13, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Familial temporal lobe epilepsy 7 Norman-Roberts syndrome Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000774897.6 First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024
Uncertain significance (Dec 15, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003680044.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: Unlikely to be causative of RELN-related lateral temporal epilepsy (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Likely benign (Jun 16, 2024)	no assertion criteria provided Method: clinical testing	RELN-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005340367.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RELN	-	-	-	-

Text-mined citations for rs143948239 ...

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 Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_005045.4(RELN):c.5961G>T (p.Lys1987Asn)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs143948239 ...