NM_001172509.2:c.347-2459G>A

Variant names:

• chr2-199384279-C-T
• rs17265387
• NM_001172509.2:c.347-2459G>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.347-2459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,178 control chromosomes in the GnomAD database, including 2,915 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 0.18 (2915 hom., cov: 32)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 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.347-2459G>A		intron	N/A	NP_001165980.1
	SATB2	NM_001172517.1		c.347-2459G>A		intron	N/A	NP_001165988.1
	SATB2	NM_015265.4		c.347-2459G>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.347-2459G>A		intron	N/A	ENSP00000401112.1
	SATB2	ENST00000260926.9	TSL:1	c.347-2459G>A		intron	N/A	ENSP00000260926.5
	SATB2	ENST00000428695.6	TSL:1	c.347-35106G>A		intron	N/A	ENSP00000388581.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27425 AN: 152060 Hom.: 2914 Cov.: 32

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.180 AC: 27436 AN: 152178 Hom.: 2915 Cov.: 32 AF XY: 0.177 AC XY: 13174 AN XY: 74402

African (AFR) AF: 0.0947 AC: 3934 AN: 41520

American (AMR) AF: 0.178 AC: 2725 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3470

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5178

South Asian (SAS) AF: 0.193 AC: 934 AN: 4828

European-Finnish (FIN) AF: 0.176 AC: 1868 AN: 10592

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16158 AN: 68000

Other (OTH) AF: 0.191 AC: 403 AN: 2110

Alfa AF: 0.209 Hom.: 1548

Bravo AF: 0.174

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.42
PhyloP100		-0.22
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: rs17265387; hg19: chr2-200249002;