NM_001172509.2:c.1387-642G>A

Variant names:

• chr2-199324600-C-T
• rs4673313
• NM_001172509.2:c.1387-642G>A

Variant summary

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

The NM_001172509.2(SATB2):​c.1387-642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,038 control chromosomes in the GnomAD database, including 46,234 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 0.76 (46234 hom., cov: 31)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 4 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=-0.36).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.89 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB2	NM_001172509.2	MANE Select	c.1387-642G>A		intron	N/A	NP_001165980.1
	SATB2	NM_001172517.1		c.1387-642G>A		intron	N/A	NP_001165988.1
	SATB2	NM_015265.4		c.1387-642G>A		intron	N/A	NP_056080.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB2	ENST00000417098.6	TSL:2 MANE Select	c.1387-642G>A		intron	N/A	ENSP00000401112.1
	SATB2	ENST00000260926.9	TSL:1	c.1387-642G>A		intron	N/A	ENSP00000260926.5
	SATB2	ENST00000428695.6	TSL:1	c.1033-642G>A		intron	N/A	ENSP00000388581.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115974 AN: 151920 Hom.: 46229 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.763 AC: 116021 AN: 152038 Hom.: 46234 Cov.: 31 AF XY: 0.767 AC XY: 57010 AN XY: 74318

African (AFR) AF: 0.531 AC: 22012 AN: 41432

American (AMR) AF: 0.767 AC: 11696 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3008 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2725 AN: 5142

South Asian (SAS) AF: 0.912 AC: 4405 AN: 4828

European-Finnish (FIN) AF: 0.920 AC: 9764 AN: 10612

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59686 AN: 67994

Other (OTH) AF: 0.782 AC: 1649 AN: 2108

Alfa AF: 0.835 Hom.: 64361

Bravo AF: 0.732

Asia WGS AF: 0.740 AC: 2574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		-0.042
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: rs4673313; hg19: chr2-200189323;