rs200409290
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS1
The NM_005045.4(RELN):c.6166C>T(p.Pro2056Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. P2056T) has been classified as Uncertain significance.
Frequency
Consequence
NM_005045.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.6166C>T | p.Pro2056Ser | missense_variant | 41/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.6166C>T | p.Pro2056Ser | missense_variant | 41/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.6166C>T | p.Pro2056Ser | missense_variant | 41/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251122Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135744
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727198
GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74456
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | The c.6166C>T (p.P2056S) alteration is located in exon 41 (coding exon 41) of the RELN gene. This alteration results from a C to T substitution at nucleotide position 6166, causing the proline (P) at amino acid position 2056 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 20, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at