chr4-185620107-C-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001395207.1(SORBS2):c.3148G>T(p.Gly1050Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,460,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SORBS2
NM_001395207.1 missense
NM_001395207.1 missense
Scores
2
10
5
Clinical Significance
Conservation
PhyloP100: 4.73
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORBS2 | NM_001395207.1 | c.3148G>T | p.Gly1050Trp | missense_variant | 20/27 | ENST00000695409.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORBS2 | ENST00000695409.1 | c.3148G>T | p.Gly1050Trp | missense_variant | 20/27 | NM_001395207.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460374Hom.: 0 Cov.: 28 AF XY: 0.0000151 AC XY: 11AN XY: 726636
GnomAD4 exome
AF:
AC:
21
AN:
1460374
Hom.:
Cov.:
28
AF XY:
AC XY:
11
AN XY:
726636
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
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
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 08, 2022 | The c.2548G>T (p.G850W) alteration is located in exon 14 (coding exon 10) of the SORBS2 gene. This alteration results from a G to T substitution at nucleotide position 2548, causing the glycine (G) at amino acid position 850 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
Benign
BayesDel_addAF
Pathogenic
D
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
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;D;D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;T;T;T;T;T;T;T;.;T
Polyphen
1.0
.;.;D;.;.;.;.;D;.;.
Vest4
MutPred
0.32
.;.;Gain of MoRF binding (P = 0.0462);.;.;.;.;.;.;.;
MVP
MPC
0.70
ClinPred
D
GERP RS
Varity_R
gMVP
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
Publications
No publications associated with this variant yet.