2-199272281-T-A

Variant names:

• chr2-199272281-T-A
• NM_001172509.2:c.2132A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001172509.2(SATB2):​c.2132A>T​(p.Tyr711Phe) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SATB2 NM_001172509.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71

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 Uncertain_significance. 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=0.07694498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATB2	NM_001172509.2	c.2132A>T	p.Tyr711Phe	missense_variant	Exon 11 of 11	ENST00000417098.6	NP_001165980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000417098.6	c.2132A>T	p.Tyr711Phe	missense_variant	Exon 11 of 11	2	NM_001172509.2	ENSP00000401112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2132A>T (p.Y711F) alteration is located in exon 12 (coding exon 10) of the SATB2 gene. This alteration results from a A to T substitution at nucleotide position 2132, causing the tyrosine (Y) at amino acid position 711 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.25
DEOGEN2	Benign	0.12	T;.;T;T;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	.;D;D;.;.;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.077	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.;.;N;.;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.010	N;.;N;N;N;N
REVEL	Benign	0.049
Sift	Benign	1.0	T;.;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0020	B;.;.;B;.;B
Vest4		0.26
MutPred		0.27		Loss of phosphorylation at Y711 (P = 0.007);.;.;Loss of phosphorylation at Y711 (P = 0.007);.;Loss of phosphorylation at Y711 (P = 0.007);
MVP		0.51
MPC		0.96
ClinPred		0.15	T
GERP RS		4.5
Varity_R		0.12
gMVP		0.12

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: chr2-200137004;