2-199380460-C-A

Variant names:

• chr2-199380460-C-A
• rs761351033
• NM_001172509.2:c.501G>T
• SATB2 p.Ala167Ala

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_001172509.2(SATB2):​c.501G>T​(p.Ala167Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A167A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SATB2 NM_001172509.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• 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: 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-0.271 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000411 (6/1461532) while in subpopulation EAS AF = 0.000126 (5/39700). AF 95% confidence interval is 0.0000491. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.501G>T	p.Ala167Ala	synonymous	Exon 5 of 11	NP_001165980.1	Q9UPW6-1
	SATB2	NM_001172517.1		c.501G>T	p.Ala167Ala	synonymous	Exon 6 of 12	NP_001165988.1	Q59FT3
	SATB2	NM_015265.4		c.501G>T	p.Ala167Ala	synonymous	Exon 6 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.501G>T	p.Ala167Ala	synonymous	Exon 5 of 11	ENSP00000401112.1	Q9UPW6-1
	SATB2	ENST00000260926.9	TSL:1	c.501G>T	p.Ala167Ala	synonymous	Exon 6 of 12	ENSP00000260926.5	Q9UPW6-1
	SATB2	ENST00000428695.6	TSL:1	c.347-31287G>T		intron	N/A	ENSP00000388581.1	Q9UPW6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461532 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727098

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111900

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.1
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs761351033;

hg19: chr2-200245183;