NM_001172509.2:c.1627delC

Variant names:

• chr2-199308872-CG-C
• rs1135401803
• NM_001172509.2:c.1627delC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001172509.2(SATB2):​c.1627delC​(p.Arg543AlafsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SATB2 NM_001172509.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.31
• Publications: 1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• SATB2 associated disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, ClinGen, PanelApp Australia

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-199308872-CG-C is Pathogenic according to our data. Variant chr2-199308872-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 431132.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1627delC	p.Arg543AlafsTer3	frameshift	Exon 10 of 11	NP_001165980.1	Q9UPW6-1
	SATB2	NM_001172517.1		c.1627delC	p.Arg543AlafsTer3	frameshift	Exon 11 of 12	NP_001165988.1	Q59FT3
	SATB2	NM_015265.4		c.1627delC	p.Arg543AlafsTer3	frameshift	Exon 11 of 12	NP_056080.1	Q9UPW6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB2	ENST00000417098.6	TSL:2 MANE Select	c.1627delC	p.Arg543AlafsTer3	frameshift	Exon 10 of 11	ENSP00000401112.1	Q9UPW6-1
	SATB2	ENST00000260926.9	TSL:1	c.1627delC	p.Arg543AlafsTer3	frameshift	Exon 11 of 12	ENSP00000260926.5	Q9UPW6-1
	SATB2	ENST00000428695.6	TSL:1	c.1273delC	p.Arg425AlafsTer3	frameshift	Exon 8 of 9	ENSP00000388581.1	Q9UPW6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Chromosome 2q32-q33 deletion syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs1135401803; hg19: chr2-200173595;