rs281875184
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_003070.5(SMARCA2):c.3475C>G(p.Arg1159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1159L) has been classified as Pathogenic.
Frequency
Consequence
NM_003070.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA2 | NM_003070.5 | c.3475C>G | p.Arg1159Gly | missense_variant | 25/34 | ENST00000349721.8 | |
SMARCA2 | NM_001289396.1 | c.3475C>G | p.Arg1159Gly | missense_variant | 25/34 | ||
SMARCA2 | NM_139045.4 | c.3475C>G | p.Arg1159Gly | missense_variant | 25/33 | ||
SMARCA2 | NM_001289397.2 | c.3301C>G | p.Arg1101Gly | missense_variant | 25/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA2 | ENST00000349721.8 | c.3475C>G | p.Arg1159Gly | missense_variant | 25/34 | 5 | NM_003070.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Nicolaides-Baraitser syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 04, 2019 | Variant summary: SMARCA2 c.3475C>G (p.Arg1159Gly) results in a non-conservative amino acid change located in the Helicase, C-terminal domain (IPR001650) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250800 control chromosomes (gnomAD). c.3475C>G has been reported in the literature in individuals affected with Nicolaides-Baraitser syndrome (e.g. VanHoudt_2012, Sousa_2014), and was detected as a de-novo mutation in at least one of these patients (VanHoudt_2012). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. In addition, p.R1159Q and p.R1159L have been reported in patients with Nicolaides-Baraitser syndrome (HGMD database). Based on the evidence outlined above, the variant was classified as pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 26, 2012 | - - |
not provided Other:1
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at