1-206393546-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BP4_Strong
The NM_015326.5(SRGAP2):c.704G>A(p.Arg235His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. R235R) has been classified as Benign.
Frequency
Genomes: not found (cov: 20)
Exomes 𝑓: 0.0000032 ( 0 hom. )
Consequence
SRGAP2
NM_015326.5 missense, splice_region
NM_015326.5 missense, splice_region
Scores
6
4
2
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
SRGAP2 (HGNC:19751): (SLIT-ROBO Rho GTPase activating protein 2) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. The encoded protein stimulates GTPase activity of Rac1, and plays a role in cortical neuron development. This locus has several paralogs on human chromosome 1 resulting from segmental duplication. While this locus itself is conserved among various species, the paralogs are found only in the genus Homo, and not in the genomes of non-human great apes. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, Dann, Eigen, phyloP100way_vertebrate, PrimateAI [when BayesDel_noAF, MetaRNN was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.009718627).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRGAP2 | NM_015326.5 | c.704G>A | p.Arg235His | missense_variant, splice_region_variant | 7/23 | ENST00000573034.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRGAP2 | ENST00000573034.8 | c.704G>A | p.Arg235His | missense_variant, splice_region_variant | 7/23 | 1 | NM_015326.5 | P5 | |
SRGAP2 | ENST00000624873.3 | c.704G>A | p.Arg235His | missense_variant, splice_region_variant | 6/22 | 1 | A1 | ||
SRGAP2 | ENST00000605610.5 | c.704G>A | p.Arg235His | missense_variant, splice_region_variant | 6/20 | 2 | |||
SRGAP2 | ENST00000419187.6 | c.245G>A | p.Arg82His | missense_variant, splice_region_variant | 4/7 | 5 |
Frequencies
GnomAD3 genomes Cov.: 20
GnomAD3 genomes
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20
GnomAD3 exomes AF: 0.00294 AC: 617AN: 209880Hom.: 0 AF XY: 0.00271 AC XY: 310AN XY: 114452
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GnomAD4 exome AF: 0.00000319 AC: 2AN: 626626Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 341334
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GnomAD4 genome Cov.: 20
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1689
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | research | Lars Feuk Lab, Uppsala University | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at