rs786201015
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001378328.1(CELSR1):c.5053_5054insTG(p.Glu1685ValfsTer22) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,460,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as risk factor (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CELSR1
NM_001378328.1 frameshift
NM_001378328.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.73
Genes affected
CELSR1 (HGNC:1850): (cadherin EGF LAG seven-pass G-type receptor 1) The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. This particular member is a developmentally regulated, neural-specific gene which plays an unspecified role in early embryogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CELSR1 | NM_001378328.1 | c.5053_5054insTG | p.Glu1685ValfsTer22 | frameshift_variant | 8/35 | ENST00000674500.2 | NP_001365257.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CELSR1 | ENST00000674500.2 | c.5053_5054insTG | p.Glu1685ValfsTer22 | frameshift_variant | 8/35 | NM_001378328.1 | ENSP00000501367 | A2 | ||
| CELSR1 | ENST00000262738.9 | c.5053_5054insTG | p.Glu1685ValfsTer22 | frameshift_variant | 8/35 | 1 | ENSP00000262738 | P4 | ||
| CELSR1 | ENST00000674359.1 | c.66_67insTG | p.Glu23ValfsTer22 | frameshift_variant | 1/10 | ENSP00000501512 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250830Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135678
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460992Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726874
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GnomAD4 genome
GnomAD4 genome
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32
Bravo
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ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neural tube defects, susceptibility to Other:1
| risk factor, no assertion criteria provided | literature only | OMIM | Jan 01, 2014 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at