chr2-199425636-A-G

Variant names:

• chr2-199425636-A-G
• rs1992950
• NM_001172509.2:c.346+7702T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172509.2(SATB2):​c.346+7702T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,960 control chromosomes in the GnomAD database, including 9,556 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9556 hom., cov: 32)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 15 publications found

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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• SATB2 associated disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB2	NM_001172509.2	MANE Select	c.346+7702T>C		intron	N/A	NP_001165980.1
	SATB2	NM_001172517.1		c.346+7702T>C		intron	N/A	NP_001165988.1
	SATB2	NM_015265.4		c.346+7702T>C		intron	N/A	NP_056080.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB2	ENST00000417098.6	TSL:2 MANE Select	c.346+7702T>C		intron	N/A	ENSP00000401112.1
	SATB2	ENST00000260926.9	TSL:1	c.346+7702T>C		intron	N/A	ENSP00000260926.5
	SATB2	ENST00000428695.6	TSL:1	c.346+7702T>C		intron	N/A	ENSP00000388581.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50932 AN: 151842 Hom.: 9535 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.336 AC: 50993 AN: 151960 Hom.: 9556 Cov.: 32 AF XY: 0.333 AC XY: 24731 AN XY: 74260

African (AFR) AF: 0.452 AC: 18696 AN: 41400

American (AMR) AF: 0.342 AC: 5218 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 962 AN: 3466

East Asian (EAS) AF: 0.615 AC: 3175 AN: 5162

South Asian (SAS) AF: 0.422 AC: 2031 AN: 4812

European-Finnish (FIN) AF: 0.214 AC: 2261 AN: 10578

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17676 AN: 67968

Other (OTH) AF: 0.355 AC: 750 AN: 2110

Alfa AF: 0.295 Hom.: 24838

Bravo AF: 0.356

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		-0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1992950; hg19: chr2-200290359;