NM_001172509.2:c.700+4332C>A

Variant names:

• chr2-199364273-G-T
• rs16831366
• NM_001172509.2:c.700+4332C>A

Variant summary

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

The NM_001172509.2(SATB2):​c.700+4332C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 152,198 control chromosomes in the GnomAD database, including 630 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 0.086 (630 hom., cov: 32)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 2 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=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 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.700+4332C>A		intron	N/A	NP_001165980.1
	SATB2	NM_001172517.1		c.700+4332C>A		intron	N/A	NP_001165988.1
	SATB2	NM_015265.4		c.700+4332C>A		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.700+4332C>A		intron	N/A	ENSP00000401112.1
	SATB2	ENST00000260926.9	TSL:1	c.700+4332C>A		intron	N/A	ENSP00000260926.5
	SATB2	ENST00000428695.6	TSL:1	c.347-15100C>A		intron	N/A	ENSP00000388581.1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13062 AN: 152078 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.0857 AC: 13045 AN: 152198 Hom.: 630 Cov.: 32 AF XY: 0.0894 AC XY: 6647 AN XY: 74386

African (AFR) AF: 0.0429 AC: 1781 AN: 41534

American (AMR) AF: 0.127 AC: 1938 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3468

East Asian (EAS) AF: 0.161 AC: 832 AN: 5158

South Asian (SAS) AF: 0.173 AC: 836 AN: 4826

European-Finnish (FIN) AF: 0.103 AC: 1090 AN: 10602

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.0836 AC: 5684 AN: 68012

Other (OTH) AF: 0.116 AC: 246 AN: 2114

Alfa AF: 0.0791 Hom.: 499

Bravo AF: 0.0840

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Benign	0.80
PhyloP100		2.6
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: rs16831366; hg19: chr2-200228996;