2-199460534-T-C

Variant names:

• chr2-199460534-T-C
• ENST00000260926.9:c.-140-2A>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_015265.4(SATB2):​c.-140-2A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SATB2 NM_015265.4 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.27

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-AS1 (HGNC:26490): (SATB2 antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.036784742 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-199460534-T-C is Pathogenic according to our data. Variant chr2-199460534-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3065059.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATB2	XM_047443775.1	c.-142A>G		5_prime_UTR_variant	Exon 1 of 11		XP_047299731.1
SATB2	XM_005246396.4	c.-88A>G		5_prime_UTR_variant	Exon 1 of 10		XP_005246453.1
SATB2	NM_001172517.1	c.-140-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 11		NP_001165988.1
SATB2	NM_015265.4	c.-140-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 11		NP_056080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATB2	ENST00000260926.9	c.-140-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 11	1		ENSP00000260926.5
SATB2	ENST00000428695.6	c.-140-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 8	1		ENSP00000388581.1
SATB2	ENST00000457245.5	c.-140-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 11	2		ENSP00000405420.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Chromosome 2q32-q33 deletion syndrome Pathogenic:1

Mar 25, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-200325257;