chr4-185593896-C-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001395207.1(SORBS2):c.3724G>T(p.Gly1242Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,603,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
SORBS2
NM_001395207.1 missense
NM_001395207.1 missense
Scores
8
5
Clinical Significance
Conservation
PhyloP100: 2.87
Genes affected
SORBS2 (HGNC:24098): (sorbin and SH3 domain containing 2) Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. They interact with the Arg/Abl binding proteins via the SH3 domains present in the carboxy end of the latter group of proteins. This gene encodes the sorbin and SH3 domain containing 2 protein. It has three C-terminal SH3 domains and an N-terminal sorbin homology (SoHo) domain that interacts with lipid raft proteins. The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that it functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.042839676).
BS2
High AC in GnomAd4 at 68 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORBS2 | NM_001395207.1 | c.3724G>T | p.Gly1242Trp | missense_variant | 25/27 | ENST00000695409.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORBS2 | ENST00000695409.1 | c.3724G>T | p.Gly1242Trp | missense_variant | 25/27 | NM_001395207.1 | |||
SORBS2-AS1 | ENST00000411847.1 | n.1682C>A | non_coding_transcript_exon_variant | 4/4 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000447 AC: 68AN: 152166Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000327 AC: 82AN: 251146Hom.: 0 AF XY: 0.000339 AC XY: 46AN XY: 135726
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GnomAD4 exome AF: 0.000227 AC: 330AN: 1451266Hom.: 0 Cov.: 26 AF XY: 0.000226 AC XY: 163AN XY: 722786
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GnomAD4 genome AF: 0.000447 AC: 68AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.000658 AC XY: 49AN XY: 74446
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2023 | The c.3124G>T (p.G1042W) alteration is located in exon 19 (coding exon 15) of the SORBS2 gene. This alteration results from a G to T substitution at nucleotide position 3124, causing the glycine (G) at amino acid position 1042 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
1.0, 1.0
.;.;.;D;.;.;.;.;D;.
Vest4
0.70, 0.62, 0.66, 0.68, 0.68, 0.69, 0.68
MVP
0.50
MPC
0.83
ClinPred
T
GERP RS
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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