4-54100663-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133267.3(GSX2):c.319G>A(p.Gly107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,192 control chromosomes in the GnomAD database, including 75,365 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 1.0 ( 75365 hom., cov: 31)

Exomes 𝑓: 1.0 ( 697774 hom. )

Failed GnomAD Quality Control

Consequence

GSX2
NM_133267.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0180

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.4659404E-7).

BP6

Variant 4-54100663-G-A is Benign according to our data. Variant chr4-54100663-G-A is described in ClinVar as [Benign]. Clinvar id is 1285310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSX2	NM_133267.3 link	c.319G>A	p.Gly107Ser	missense_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.319G>A	p.Gly107Ser	missense_variant	Exon 1 of 2	1	NM_133267.3	ENSP00000319118.2	Q9BZM3
ENSG00000282278	ENST00000507166.5 link	c.1018-174262G>A		intron_variant	Intron 12 of 23	2		ENSP00000423325.1	A0A0B4J203
GSX2	ENST00000503800.1 link	c.319G>A	p.Gly107Ser	missense_variant	Exon 1 of 2	5		ENSP00000422213.1	D6R903
GSX2	ENST00000507839.1 link	n.115-919G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.995

AC:

151338

AN:

152074

Hom.:

75307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.983

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.997

GnomAD3 exomes

AF:

0.999

AC:

148852

AN:

149028

Hom.:

74339

AF XY:

0.999

AC XY:

79504

AN XY:

79582

show subpopulations

Gnomad AFR exome

AF:

0.982

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.999

AC:

1396288

AN:

1397032

Hom.:

697774

Cov.:

AF XY:

1.00

AC XY:

688825

AN XY:

689134

show subpopulations

Gnomad4 AFR exome

AF:

0.980

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

AF:

0.995

AC:

151455

AN:

152192

Hom.:

75365

Cov.:

AF XY:

0.995

AC XY:

74054

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.983

Gnomad4 AMR

AF:

0.999

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.997

Alfa

AF:

0.999

Hom.:

115595

Bravo

AF:

0.994

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.986

AC:

3893

ESP6500EA

AF:

1.00

AC:

7589

ExAC

AF:

0.997

AC:

63757

Asia WGS

AF:

0.999

AC:

3470

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.077

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.31

T;.;T

MetaRNN

Benign

5.5e-7

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.23

N;N;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.41

.;N;N

REVEL

Benign

0.091

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.020

MPC

0.78

ClinPred

0.00061

GERP RS

1.4

Varity_R

0.038

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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