12-64043505-T-TAG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020762.4(SRGAP1):c.731_732insAG(p.Leu245AlafsTer2) 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 Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SRGAP1
NM_020762.4 frameshift
NM_020762.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.981
Genes affected
SRGAP1 (HGNC:17382): (SLIT-ROBO Rho GTPase activating protein 1) The protein encoded by this gene is a GTPase activator, working with the GTPase CDC42 to negatively regulate neuronal migration. The encoded protein interacts with the transmembrane receptor ROBO1 to inactivate CDC42. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRGAP1 | NM_020762.4 | c.731_732insAG | p.Leu245AlafsTer2 | frameshift_variant | 6/22 | ENST00000355086.8 | |
SRGAP1 | NM_001346201.2 | c.731_732insAG | p.Leu245AlafsTer2 | frameshift_variant | 6/22 | ||
SRGAP1 | XM_024449096.2 | c.731_732insAG | p.Leu245AlafsTer2 | frameshift_variant | 6/14 | ||
SRGAP1 | XM_024449097.2 | c.731_732insAG | p.Leu245AlafsTer2 | frameshift_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRGAP1 | ENST00000355086.8 | c.731_732insAG | p.Leu245AlafsTer2 | frameshift_variant | 6/22 | 1 | NM_020762.4 | A1 | |
ENST00000535594.1 | n.134-566_134-565insCT | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Thyroid cancer, nonmedullary, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Feb 19, 2020 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at