Variant 2-199349049-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001172509.2(SATB2):c.825A>C(p.Gln275His) 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 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SATB2
NM_001172509.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.754

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 links:

SATB2 (HGNC:):

SATB2 links:

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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 in gene, where missense usually causes diseases (based on misZ statistic), SATB2. . Gene score misZ 4.0511 (greater than the threshold 3.09). Trascript score misZ 5.5168 (greater than threshold 3.09). GenCC has associacion of gene with chromosome 2q32-q33 deletion syndrome, SATB2 associated disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.15037647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SATB2	NM_001172509.2 linkuse as main transcript	c.825A>C	p.Gln275His	missense_variant	7/11	ENST00000417098.6	NP_001165980.1	Q9UPW6-1A0A024R3U6B3KPQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000417098.6 linkuse as main transcript	c.825A>C	p.Gln275His	missense_variant	7/11	2	NM_001172509.2	ENSP00000401112.1		Q9UPW6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251392

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;T;T;.;T

Eigen

Benign

0.018

Eigen_PC

Benign

0.043

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.86

.;D;D;.;.;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;.;.;L;.;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

N;.;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.035

D;.;D;D;D;D

Sift4G

Uncertain

0.047

D;T;D;D;T;D

Polyphen

0.98

D;.;.;D;.;D

Vest4

0.24

MutPred

0.13

Gain of glycosylation at S274 (P = 0.0618);.;.;Gain of glycosylation at S274 (P = 0.0618);.;Gain of glycosylation at S274 (P = 0.0618);

MVP

0.55

MPC

0.99

ClinPred

0.50

GERP RS

3.0

Varity_R

0.069

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over