rs796052242
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_152641.4(ARID2):c.1028T>A(p.Leu343Ter) variant causes a stop gained change. 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ARID2
NM_152641.4 stop_gained
NM_152641.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 6.11
Genes affected
ARID2 (HGNC:18037): (AT-rich interaction domain 2) This gene encodes a member of the AT-rich interactive domain (ARID)-containing family of DNA-binding proteins. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. This protein functions as a subunit of the polybromo- and BRG1-associated factor or PBAF (SWI/SNF-B) chromatin remodeling complex which facilitates ligand-dependent transcriptional activation by nuclear receptors. Mutations in this gene are associated with hepatocellular carcinomas. A pseudogene of this gene is found on chromosome1. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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;
PP5
?
Variant 12-45837325-T-A is Pathogenic according to our data. Variant chr12-45837325-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 448916.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-45837325-T-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARID2 | NM_152641.4 | c.1028T>A | p.Leu343Ter | stop_gained | 9/21 | ENST00000334344.11 | |
LOC105369745 | XR_944892.3 | n.289+2527A>T | intron_variant, non_coding_transcript_variant | ||||
ARID2 | NM_001347839.2 | c.1028T>A | p.Leu343Ter | stop_gained | 9/20 | ||
ARID2 | XM_047428489.1 | c.1028T>A | p.Leu343Ter | stop_gained | 9/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARID2 | ENST00000334344.11 | c.1028T>A | p.Leu343Ter | stop_gained | 9/21 | 1 | NM_152641.4 | P1 | |
ARID2 | ENST00000422737.7 | c.1028T>A | p.Leu343Ter | stop_gained | 9/20 | 1 | |||
ARID2 | ENST00000479608.5 | c.236T>A | p.Leu79Ter | stop_gained, NMD_transcript_variant | 2/15 | 1 | |||
ARID2 | ENST00000480128.1 | n.52T>A | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Coffin-Siris syndrome 6 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 14, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 15, 2018 | This variant is interpreted as Likely Pathogenic, for Coffin-Siris syndrome 6, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Strong => PVS1 downgraded in strength to Strong. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at