rs771681966
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP6_Moderate
The NM_005045.4(RELN):āc.8261T>Gā(p.Ile2754Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
RELN
NM_005045.4 missense
NM_005045.4 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 7.73
Genes affected
RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RELN. . Gene score misZ 2.2497 (greater than the threshold 3.09). Trascript score misZ 4.2638 (greater than threshold 3.09). GenCC has associacion of gene with ankylosing spondylitis, lissencephaly with cerebellar hypoplasia, Norman-Roberts syndrome, complex neurodevelopmental disorder, autosomal dominant epilepsy with auditory features, familial temporal lobe epilepsy 7.
BP6
Variant 7-103510864-A-C is Benign according to our data. Variant chr7-103510864-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 542563.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.8261T>G | p.Ile2754Ser | missense_variant | 51/65 | ENST00000428762.6 | NP_005036.2 | |
SLC26A5-AS1 | NR_110141.1 | n.1487-1905A>C | intron_variant, non_coding_transcript_variant | |||||
RELN | NM_173054.3 | c.8261T>G | p.Ile2754Ser | missense_variant | 51/64 | NP_774959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.8261T>G | p.Ile2754Ser | missense_variant | 51/65 | 5 | NM_005045.4 | ENSP00000392423 | P5 | |
SLC26A5-AS1 | ENST00000422488.1 | n.1487-1905A>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251334Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135844
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461338Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727040
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 14, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;.
Vest4
MutPred
Gain of disorder (P = 0.0404);Gain of disorder (P = 0.0404);Gain of disorder (P = 0.0404);
MVP
MPC
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at