chr2-199368710-G-GAA

Variant names:

• chr2-199368710-G-GAA
• rs199978702
• NM_001172509.2:c.598-5_598-4dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001172509.2(SATB2):​c.598-5_598-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,318,832 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SATB2 NM_001172509.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.598-5_598-4dupTT		splice_region intron	N/A	NP_001165980.1
	SATB2	NM_001172517.1		c.598-5_598-4dupTT		splice_region intron	N/A	NP_001165988.1
	SATB2	NM_015265.4		c.598-5_598-4dupTT		splice_region 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.598-5_598-4dupTT		splice_region intron	N/A	ENSP00000401112.1
	SATB2	ENST00000260926.9	TSL:1	c.598-5_598-4dupTT		splice_region intron	N/A	ENSP00000260926.5
	SATB2	ENST00000428695.6	TSL:1	c.347-19539_347-19538dupTT		intron	N/A	ENSP00000388581.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 19 AN: 1318832 Hom.: 0 Cov.: 24 AF XY: 0.0000182 AC XY: 12 AN XY: 659524

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29656

American (AMR) AF: 0.00 AC: 0 AN: 40146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23926

East Asian (EAS) AF: 0.00 AC: 0 AN: 36476

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5262

European-Non Finnish (NFE) AF: 0.0000180 AC: 18 AN: 1000956

Other (OTH) AF: 0.00 AC: 0 AN: 54536

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199978702; hg19: chr2-200233433;