chr2-199311320-G-T

Variant names:

• chr2-199311320-G-T
• rs4675475
• NM_001172509.2:c.1543-2363C>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.1543-2363C>A variant causes a intron change. The variant allele was found at a frequency of 0.597 in 151,890 control chromosomes in the GnomAD database, including 31,262 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 0.60 (31262 hom., cov: 30)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22
• Publications: 6 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=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATB2	NM_001172509.2	c.1543-2363C>A		intron_variant	Intron 9 of 10	ENST00000417098.6	NP_001165980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000417098.6	c.1543-2363C>A		intron_variant	Intron 9 of 10	2	NM_001172509.2	ENSP00000401112.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90710 AN: 151768 Hom.: 31277 Cov.: 30

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.597 AC: 90694 AN: 151890 Hom.: 31262 Cov.: 30 AF XY: 0.601 AC XY: 44604 AN XY: 74214

African (AFR) AF: 0.251 AC: 10392 AN: 41426

American (AMR) AF: 0.654 AC: 9972 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2604 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1885 AN: 5144

South Asian (SAS) AF: 0.592 AC: 2846 AN: 4804

European-Finnish (FIN) AF: 0.808 AC: 8516 AN: 10546

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52175 AN: 67934

Other (OTH) AF: 0.629 AC: 1325 AN: 2108

Alfa AF: 0.677 Hom.: 6334

Bravo AF: 0.566

Asia WGS AF: 0.440 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.85
PhyloP100		4.2
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: rs4675475; hg19: chr2-200176043;