2-199292872-T-G

Variant names:

• chr2-199292872-T-G
• rs1446636
• NM_001172509.2:c.1740+15888A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001172509.2(SATB2):​c.1740+15888A>C variant causes a intron change. The variant allele was found at a frequency of 0.792 in 152,076 control chromosomes in the GnomAD database, including 49,292 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 0.79 (49292 hom., cov: 32)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.884 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.1740+15888A>C		intron	N/A	NP_001165980.1
	SATB2	NM_001172517.1		c.1740+15888A>C		intron	N/A	NP_001165988.1
	SATB2	NM_015265.4		c.1740+15888A>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.1740+15888A>C		intron	N/A	ENSP00000401112.1
	SATB2	ENST00000260926.9	TSL:1	c.1740+15888A>C		intron	N/A	ENSP00000260926.5
	SATB2	ENST00000428695.6	TSL:1	c.1386+15888A>C		intron	N/A	ENSP00000388581.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120392 AN: 151958 Hom.: 49285 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.792 AC: 120434 AN: 152076 Hom.: 49292 Cov.: 32 AF XY: 0.795 AC XY: 59135 AN XY: 74352

African (AFR) AF: 0.566 AC: 23469 AN: 41464

American (AMR) AF: 0.856 AC: 13079 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3035 AN: 3468

East Asian (EAS) AF: 0.837 AC: 4325 AN: 5170

South Asian (SAS) AF: 0.801 AC: 3859 AN: 4820

European-Finnish (FIN) AF: 0.888 AC: 9402 AN: 10590

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60471 AN: 67978

Other (OTH) AF: 0.807 AC: 1701 AN: 2108

Alfa AF: 0.860 Hom.: 65425

Bravo AF: 0.779

Asia WGS AF: 0.760 AC: 2641 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.83
PhyloP100		4.0
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: rs1446636; hg19: chr2-200157595;