2-218662244-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001079866.2(BCS1L):āc.703G>Cā(p.Gly235Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ).
Frequency
Consequence
NM_001079866.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCS1L | NM_001079866.2 | c.703G>C | p.Gly235Arg | missense_variant | 5/8 | ENST00000359273.8 | NP_001073335.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BCS1L | ENST00000359273.8 | c.703G>C | p.Gly235Arg | missense_variant | 5/8 | 1 | NM_001079866.2 | ENSP00000352219.3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251424Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461740Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727188
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74340
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 09, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 235 of the BCS1L protein (p.Gly235Arg). This variant is present in population databases (rs368486097, gnomAD 0.004%). This missense change has been observed in individual(s) with Bjornstad syndrome (PMID: 28322498). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1442140). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BCS1L protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at