rs281875197
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP2PP3_StrongPP5
The NM_003070.5(SMARCA2):c.3314G>A(p.Arg1105His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1105L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003070.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA2 | NM_003070.5 | c.3314G>A | p.Arg1105His | missense_variant | 24/34 | ENST00000349721.8 | |
SMARCA2 | NM_001289396.1 | c.3314G>A | p.Arg1105His | missense_variant | 24/34 | ||
SMARCA2 | NM_139045.4 | c.3314G>A | p.Arg1105His | missense_variant | 24/33 | ||
SMARCA2 | NM_001289397.2 | c.3140G>A | p.Arg1047His | missense_variant | 24/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA2 | ENST00000349721.8 | c.3314G>A | p.Arg1105His | missense_variant | 24/34 | 5 | NM_003070.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Nicolaides-Baraitser syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 01, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Sep 02, 2020 | This variant was identified as de novo (maternity and paternity confirmed). - |
Blepharophimosis-impaired intellectual development syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 01, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 16, 2019 | The p.R1105H variant (also known as c.3314G>A), located in coding exon 23 of the SMARCA2 gene, results from a G to A substitution at nucleotide position 3314. The arginine at codon 1105 is replaced by histidine, an amino acid with highly similar properties. This variant has been identified as de novo in an individual with SMARCA2-consistent phentoype (Santen GW et al. Hum. Mutat., 2013 Nov;34:1519-28). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at