rs2278141

Variant names:

• chr4-54101191-C-A
• rs2278141
• NM_133267.3:c.574+273C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133267.3(GSX2):​c.574+273C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,116 control chromosomes in the GnomAD database, including 25,011 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 0.55 (25011 hom., cov: 32)
• Consequence: GSX2 NM_133267.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 3 publications found

Genes affected

GSX2 (HGNC:24959): (GS homeobox 2) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including nervous system development; positive regulation of Notch signaling pathway; and regulation of respiratory gaseous exchange by nervous system process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GSX2 Gene-Disease associations (from GenCC):

• diencephalic-mesencephalic junction dysplasia syndrome 2

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133267.3. 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
	GSX2	NM_133267.3	MANE Select	c.574+273C>A		intron	N/A	NP_573574.2	Q9BZM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSX2	ENST00000326902.7	TSL:1 MANE Select	c.574+273C>A		intron	N/A	ENSP00000319118.2	Q9BZM3
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-173734C>A		intron	N/A	ENSP00000423325.1	A0A0B4J203
	GSX2	ENST00000503800.1	TSL:5	c.364-391C>A		intron	N/A	ENSP00000422213.1	D6R903

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84309 AN: 151996 Hom.: 24996 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.554 AC: 84340 AN: 152116 Hom.: 25011 Cov.: 32 AF XY: 0.560 AC XY: 41667 AN XY: 74362

African (AFR) AF: 0.340 AC: 14088 AN: 41476

American (AMR) AF: 0.668 AC: 10216 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.832 AC: 4278 AN: 5142

South Asian (SAS) AF: 0.649 AC: 3125 AN: 4818

European-Finnish (FIN) AF: 0.645 AC: 6841 AN: 10598

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41858 AN: 67998

Other (OTH) AF: 0.568 AC: 1200 AN: 2112

Alfa AF: 0.566 Hom.: 3810

Bravo AF: 0.549

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2278141; hg19: chr4-54967358;