NM_001172509.2:c.347-155C>T

Variant names:

• chr2-199381975-G-A
• rs17199393
• NM_001172509.2:c.347-155C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001172509.2(SATB2):​c.347-155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 152,264 control chromosomes in the GnomAD database, including 136 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 0.037 (136 hom., cov: 32)
• Consequence: SATB2 NM_001172509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATB2	NM_001172509.2	c.347-155C>T		intron_variant	Intron 3 of 10	ENST00000417098.6	NP_001165980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000417098.6	c.347-155C>T		intron_variant	Intron 3 of 10	2	NM_001172509.2	ENSP00000401112.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5710 AN: 152146 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.00960

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0375 AC: 5705 AN: 152264 Hom.: 136 Cov.: 32 AF XY: 0.0363 AC XY: 2700 AN XY: 74444

African (AFR) AF: 0.00958 AC: 398 AN: 41560

American (AMR) AF: 0.0522 AC: 798 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4826

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3553 AN: 68020

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0482 Hom.: 82

Bravo AF: 0.0380

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		1.4
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: rs17199393; hg19: chr2-200246698;