rs201044262
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP2PP3BS1_Supporting
The NM_005045.4(RELN):c.2015C>T(p.Pro672Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P672R) has been classified as Uncertain significance.
Frequency
Consequence
NM_005045.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.2015C>T | p.Pro672Leu | missense_variant | 17/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.2015C>T | p.Pro672Leu | missense_variant | 17/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.2015C>T | p.Pro672Leu | missense_variant | 17/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152046Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000159 AC: 40AN: 250800Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135522
GnomAD4 exome AF: 0.000158 AC: 231AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.000166 AC XY: 121AN XY: 727058
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74270
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2023 | Reported in two individuals within a single family with lateral temporal epilepsy as well as auditory and/or aphasic seizures in published literature (Dazzo et al., 2015); Observed in the heterozygous state in one patient with epilepsy and multiple minor anomalies in published literature (Balicza et al., 2019); the RELN variant is inherited from the patient's unaffected father; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 29755699, 36011376, 31134136, 26046367, 27493482) - |
Familial temporal lobe epilepsy 7 Uncertain:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Apr 02, 2020 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3,BS2. - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7;C4551957:Epilepsy, familial temporal lobe, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Norman-Roberts syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Goettingen | May 15, 2018 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Seizure Benign:1
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Strasbourg University Hospital | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at