rs1555774702
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001387283.1(SMARCA4):c.2329del(p.Leu777TrpfsTer54) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SMARCA4
NM_001387283.1 frameshift
NM_001387283.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.571
Genes affected
SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is 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. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
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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 19-11013001-TC-T is Pathogenic according to our data. Variant chr19-11013001-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 537835.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.2329del | p.Leu777TrpfsTer54 | frameshift_variant | 16/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.2329del | p.Leu777TrpfsTer54 | frameshift_variant | 16/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.2329del | p.Leu777TrpfsTer54 | frameshift_variant | 16/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.2329del | p.Leu777TrpfsTer54 | frameshift_variant | 16/35 | 1 | NM_003072.5 | P4 | |
ENST00000587831.1 | n.29-1748del | intron_variant, non_coding_transcript_variant | 5 |
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: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2017 | This variant has not been reported in the literature in individuals with SMARCA4-related disease. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SMARCA4 are known to be pathogenic (PMID: 24658001, 24658002). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu777Trpfs*54) in the SMARCA4 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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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