Genetic Variant GSX2:p.Ser52Ser (chr4-54100500-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_133267.3(GSX2):c.156C>T(p.Ser52Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,613,098 control chromosomes in the GnomAD database, including 312,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24934 hom., cov: 31)

Exomes 𝑓: 0.62 ( 287701 hom. )

Consequence

GSX2
NM_133267.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.380

Variant links:

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 links:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 4-54100500-C-T is Benign according to our data. Variant chr4-54100500-C-T is described in ClinVar as [Benign]. Clinvar id is 1182813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSX2	NM_133267.3 link	c.156C>T	p.Ser52Ser	synonymous_variant	Exon 1 of 2	ENST00000326902.7	NP_573574.2	Q9BZM3B2LYG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSX2	ENST00000326902.7 link	c.156C>T	p.Ser52Ser	synonymous_variant	Exon 1 of 2	1	NM_133267.3	ENSP00000319118.2	Q9BZM3
ENSG00000282278	ENST00000507166.5 link	c.1018-174425C>T		intron_variant	Intron 12 of 23	2		ENSP00000423325.1	A0A0B4J203
GSX2	ENST00000503800.1 link	c.156C>T	p.Ser52Ser	synonymous_variant	Exon 1 of 2	5		ENSP00000422213.1	D6R903
GSX2	ENST00000507839.1 link	n.114+864C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84166

AN:

151816

Hom.:

24920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.831

Gnomad SAS

AF:

0.649

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.566

GnomAD3 exomes

AF:

0.641

AC:

159009

AN:

248174

Hom.:

52596

AF XY:

0.640

AC XY:

86205

AN XY:

134666

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.774

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.834

Gnomad SAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.624

AC:

911193

AN:

1461164

Hom.:

287701

Cov.:

AF XY:

0.624

AC XY:

453771

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.762

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.825

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.647

Gnomad4 NFE exome

AF:

0.620

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.554

AC:

84195

AN:

151934

Hom.:

24934

Cov.:

AF XY:

0.560

AC XY:

41578

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.668

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.830

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.616

Gnomad4 OTH

AF:

0.568

Alfa

AF:

0.582

Hom.:

12998

Bravo

AF:

0.549

Asia WGS

AF:

0.695

AC:

2416

AN:

3478

EpiCase

AF:

0.610

EpiControl

AF:

0.611

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diencephalic-mesencephalic junction dysplasia syndrome 2

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over