rs3793510
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_003070.5(SMARCA2):āc.4247G>Cā(p.Gly1416Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,614,096 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 1 hom. )
Consequence
SMARCA2
NM_003070.5 missense
NM_003070.5 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.84
Genes affected
SMARCA2 (HGNC:11098): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SMARCA2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.02216801).
BP6
?
Variant 9-2170466-G-C is Benign according to our data. Variant chr9-2170466-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 914998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000854 (13/152274) while in subpopulation EAS AF= 0.00251 (13/5184). AF 95% confidence interval is 0.00148. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA2 | NM_003070.5 | c.4247G>C | p.Gly1416Ala | missense_variant | 29/34 | ENST00000349721.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA2 | ENST00000349721.8 | c.4247G>C | p.Gly1416Ala | missense_variant | 29/34 | 5 | NM_003070.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251398Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135860
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GnomAD4 exome AF: 0.000137 AC: 200AN: 1461822Hom.: 1 Cov.: 29 AF XY: 0.000116 AC XY: 84AN XY: 727210
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Nicolaides-Baraitser syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;N;.;.
REVEL
Benign
Sift
Benign
T;T;.;.;T;.;.
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
D;D;.;.;.;.;.
Vest4
MVP
MPC
0.15
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at