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GeneBe

2-199272283-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001172509.2(SATB2):c.2130G>C(p.Met710Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M710K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SATB2
NM_001172509.2 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.80
Variant links:
Genes affected
SATB2 (HGNC:21637): (SATB homeobox 2) This gene encodes a DNA binding protein that specifically binds nuclear matrix attachment regions. The encoded protein is involved in transcription regulation and chromatin remodeling. Defects in this gene are associated with isolated cleft palate and cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Feb 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SATB2
BP4
Computational evidence support a benign effect (MetaRNN=0.11482346).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SATB2NM_001172509.2 linkuse as main transcriptc.2130G>C p.Met710Ile missense_variant 11/11 ENST00000417098.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SATB2ENST00000417098.6 linkuse as main transcriptc.2130G>C p.Met710Ile missense_variant 11/112 NM_001172509.2 P1Q9UPW6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMay 13, 2022Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Chromosome 2q32-q33 deletion syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeAug 17, 2023In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SATB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1385085). This variant has not been reported in the literature in individuals affected with SATB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 710 of the SATB2 protein (p.Met710Ile). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
Cadd
Benign
21
Dann
Benign
0.96
DEOGEN2
Benign
0.11
T;.;T;T;.;T
Eigen
Benign
-0.16
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.83
D
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.11
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.;.;N;.;N
MutationTaster
Benign
0.90
D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.56
N;.;N;N;N;N
REVEL
Benign
0.069
Sift
Benign
0.38
T;.;T;T;T;T
Sift4G
Benign
0.51
T;T;T;T;T;T
Polyphen
0.0
B;.;.;B;.;B
Vest4
0.19
MutPred
0.33
Gain of sheet (P = 0.0221);.;.;Gain of sheet (P = 0.0221);.;Gain of sheet (P = 0.0221);
MVP
0.22
MPC
1.2
ClinPred
0.51
D
GERP RS
5.6
Varity_R
0.18
gMVP
0.085

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-200137006; API