2-199272284-A-T

Position:

• chr2-199272284-A-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.2129T>A​(p.Met710Lys) 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. 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: 6.63

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 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=0.24880123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SATB2	NM_001172509.2	c.2129T>A	p.Met710Lys	missense_variant	11/11	ENST00000417098.6	NP_001165980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000417098.6	c.2129T>A	p.Met710Lys	missense_variant	11/11	2	NM_001172509.2	ENSP00000401112	P1

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Sep 22, 2023

Variant summary: SATB2 c.2129T>A (p.Met710Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251052 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2129T>A in individuals affected with SATB2 Associated Disorder and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T;.;T;T;.;T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;D;.;.;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.;N;.;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.5	N;.;N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D;.;D;D;D;D
Sift4G	Uncertain	0.041	D;D;D;D;D;D
Polyphen		0.0090	B;.;.;B;.;B
Vest4		0.52
MutPred		0.41		Gain of ubiquitination at M710 (P = 0.009);.;.;Gain of ubiquitination at M710 (P = 0.009);.;Gain of ubiquitination at M710 (P = 0.009);
MVP		0.57
MPC		1.6
ClinPred		0.80	D
GERP RS		5.6
Varity_R		0.68
gMVP		0.40

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: chr2-200137007;