rs766855879

Positions:

• chr2-199349142-G-C
• chr2-199349142-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Moderate BP6_Moderate BS2

The NM_001172509.2(SATB2):​c.732C>G​(p.Asp244Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SATB2 NM_001172509.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.69

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• 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). The gene has 38 curated pathogenic missense variants (we use a threshold of 10). The gene has 65 curated benign missense variants. GenCC has associacion of the gene with chromosome 2q32-q33 deletion syndrome, SATB2 associated disorder.
• BP4: Computational evidence support a benign effect (MetaRNN=0.16713047).
• BP6: Variant 2-199349142-G-C is Benign according to our data. Variant chr2-199349142-G-C is described in ClinVar as [Benign]. Clinvar id is 581640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SATB2	NM_001172509.2	c.732C>G	p.Asp244Glu	missense_variant	7/11	ENST00000417098.6	NP_001165980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000417098.6	c.732C>G	p.Asp244Glu	missense_variant	7/11	2	NM_001172509.2	ENSP00000401112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250786 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135520

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461548 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727058

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Chromosome 2q32-q33 deletion syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Benign	0.81
DEOGEN2	Benign	0.19	T;.;T;T;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.0057
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	.;T;T;.;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;.;.;N;.;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.61	N;.;N;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.76	T;.;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.0	B;.;.;B;.;B
Vest4		0.088
MutPred		0.27		Loss of sheet (P = 0.0817);.;.;Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);
MVP		0.53
MPC		0.98
ClinPred		0.23	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.26

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

Other links and lift over

dbSNP: rs766855879; hg19: chr2-200213865;