NM_005045.4(RELN):c.9976C>T (p.Arg3326Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 31, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003766808.1

Allele description [Variation Report for NM_005045.4(RELN):c.9976C>T (p.Arg3326Ter)]

NM_005045.4(RELN):c.9976C>T (p.Arg3326Ter)

Genes:

SLC26A5-AS1:SLC26A5 antisense RNA 1 [Gene - HGNC]
RELN:reelin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_005045.4(RELN):c.9976C>T (p.Arg3326Ter)

HGVS:

NC_000007.14:g.103486204G>A
NG_011877.2:g.508313C>T
NM_005045.4:c.9976C>TMANE SELECT
NM_173054.3:c.9976C>T
NP_005036.2:p.Arg3326Ter
NP_774959.1:p.Arg3326Ter
NC_000007.13:g.103126651G>A
NM_005045.3:c.9976C>T

Protein change:

R3326*

Links:

dbSNP: rs751409835

NCBI 1000 Genomes Browser:

rs751409835

Molecular consequence:

NM_005045.4:c.9976C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_173054.3:c.9976C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Norman-Roberts syndrome (LIS2)
Synonyms:: Lissencephaly 2; Lissencephaly syndrome Norman-Roberts type; Lissencephaly 2 (Norman-Roberts type)
Identifiers:: MONDO: MONDO:0009760; MedGen: C0796089; Orphanet: 89844; OMIM: 257320

Name:: Familial temporal lobe epilepsy 7
Identifiers:: MONDO: MONDO:0014639; MedGen: C4225327; Orphanet: 101046; OMIM: 616436

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004592972	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 31, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 29358611, 10973257, 26046367, 28454995, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004592972

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 31, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.

Bobbili DR, Lal D, May P, Reinthaler EM, Jabbari K, Thiele H, Nothnagel M, Jurkowski W, Feucht M, Nürnberg P, Lerche H, Zimprich F, Krause R, Neubauer BA, Reinthaler EM, Zimprich F, Feucht M, Steinböck H, Neophytou B, Geldner J, Gruber-Sedlmayr U, Haberlandt E, et al.

Eur J Hum Genet. 2018 Feb;26(2):258-264. doi: 10.1038/s41431-017-0034-x. Epub 2018 Jan 22.

PubMed [citation]

PMID:: 29358611
PMCID:: PMC5839048

Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations.

Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA.

Nat Genet. 2000 Sep;26(1):93-6. Erratum in: Nat Genet 2001 Feb;27(2):225.

PubMed [citation]

PMID:: 10973257

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004592972.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 433105). This premature translational stop signal has been observed in individual(s) with RELN-related conditions (PMID: 29358611). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg3326*) in the RELN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RELN are known to be pathogenic (PMID: 10973257, 26046367, 28454995).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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