rs1553538875

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The NM_001172509.2(SATB2):​c.2116G>A​(p.Gly706Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,210 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SATB2
NM_001172509.2 missense

Scores

4
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.84
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 Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the SATB2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 38 curated pathogenic missense variants (we use a threshold of 10). The gene has 65 curated benign missense variants. Gene score misZ: 4.0511 (above the threshold of 3.09). Trascript score misZ: 5.5168 (above the threshold of 3.09). GenCC associations: The gene is linked to chromosome 2q32-q33 deletion syndrome, SATB2 associated disorder.
BP4
Computational evidence support a benign effect (MetaRNN=0.10722983).
BP6
Variant 2-199272297-C-T is Benign according to our data. Variant chr2-199272297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 537271.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SATB2NM_001172509.2 linkc.2116G>A p.Gly706Ser missense_variant Exon 11 of 11 ENST00000417098.6 NP_001165980.1 Q9UPW6-1A0A024R3U6B3KPQ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SATB2ENST00000417098.6 linkc.2116G>A p.Gly706Ser missense_variant Exon 11 of 11 2 NM_001172509.2 ENSP00000401112.1 Q9UPW6-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Chromosome 2q32-q33 deletion syndrome Benign:1
Nov 06, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;.;T;T;.;T
Eigen
Benign
-0.027
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
.;D;D;.;.;D
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.11
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.55
N;.;.;N;.;N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.16
N;.;N;N;N;N
REVEL
Benign
0.032
Sift
Benign
0.28
T;.;T;T;T;T
Sift4G
Benign
0.85
T;T;T;T;T;T
Polyphen
0.025
B;.;.;B;.;B
Vest4
0.24
MutPred
0.34
Gain of phosphorylation at G706 (P = 0.0012);.;.;Gain of phosphorylation at G706 (P = 0.0012);.;Gain of phosphorylation at G706 (P = 0.0012);
MVP
0.082
MPC
1.0
ClinPred
0.83
D
GERP RS
5.6
Varity_R
0.12
gMVP
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553538875; hg19: chr2-200137020; COSMIC: COSV53486292; API