Genetic Variant SATB2:p.Ala720Thr (chr2-199272255-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172509.2(SATB2):c.2158G>A(p.Ala720Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SATB2
NM_001172509.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.221

Publications

0 publications found

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]

SATB2 Gene-Disease associations (from GenCC):

chromosome 2q32-q33 deletion syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
SATB2 associated disorder
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, ClinGen, PanelApp Australia

SATB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052811533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172509.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SATB2	NM_001172509.2	MANE Select	c.2158G>A	p.Ala720Thr	missense	Exon 11 of 11	NP_001165980.1	Q9UPW6-1
SATB2	NM_001172517.1		c.2158G>A	p.Ala720Thr	missense	Exon 12 of 12	NP_001165988.1	Q59FT3
SATB2	NM_015265.4		c.2158G>A	p.Ala720Thr	missense	Exon 12 of 12	NP_056080.1	Q9UPW6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SATB2	ENST00000417098.6	TSL:2 MANE Select	c.2158G>A	p.Ala720Thr	missense	Exon 11 of 11	ENSP00000401112.1	Q9UPW6-1
SATB2	ENST00000260926.9	TSL:1	c.2158G>A	p.Ala720Thr	missense	Exon 12 of 12	ENSP00000260926.5	Q9UPW6-1
SATB2	ENST00000428695.6	TSL:1	c.1804G>A	p.Ala602Thr	missense	Exon 9 of 9	ENSP00000388581.1	Q9UPW6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Chromosome 2q32-q33 deletion syndrome (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0091

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

0.22

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.58

REVEL

Benign

0.040

Sift

Uncertain

0.011

Sift4G

Uncertain

0.015

Polyphen

0.0020

Vest4

0.074

MutPred

0.24

Gain of phosphorylation at A720 (P = 0.0108)

MVP

0.34

MPC

1.0

ClinPred

0.13

GERP RS

4.7

Varity_R

0.070

gMVP

0.079

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over