NM_032575.3:c.70C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_032575.3(GLIS2):c.70C>A(p.Arg24Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,142 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 14 hom., cov: 32)

Exomes 𝑓: 0.011 ( 102 hom. )

Consequence

GLIS2
NM_032575.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.927

Variant links:

Genes affected

GLIS2 (HGNC:29450): (GLIS family zinc finger 2) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein's C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120. Mutations in this gene cause nephronophthisis (NPHP), an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys.[provided by RefSeq, Jan 2010]

GLIS2 links:

PAM16 (HGNC:29679): (presequence translocase associated motor 16) This gene encodes a mitochondrial protein involved in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. This protein also plays a role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix and may be important in reactive oxygen species (ROS) homeostasis. Mutations in this gene cause Megarbane-Dagher-Melike type spondylometaphyseal dysplasia, an early lethal skeletal dysplasia characterized by short stature, developmental delay and other skeletal abnormalities. [provided by RefSeq, May 2017]

PAM16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 16-4332350-C-A is Benign according to our data. Variant chr16-4332350-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 215539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-4332350-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.927 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS2	NM_032575.3 link	c.70C>A	p.Arg24Arg	synonymous_variant	Exon 2 of 7	ENST00000433375.2	NP_115964.2	Q9BZE0
GLIS2	NM_001318918.2 link	c.70C>A	p.Arg24Arg	synonymous_variant	Exon 3 of 8		NP_001305847.1	Q9BZE0B3KTH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLIS2	ENST00000433375.2 link	c.70C>A	p.Arg24Arg	synonymous_variant	Exon 2 of 7	1	NM_032575.3	ENSP00000395547.1	Q9BZE0
GLIS2	ENST00000262366.7 link	c.70C>A	p.Arg24Arg	synonymous_variant	Exon 3 of 8	2		ENSP00000262366.3	Q9BZE0
PAM16	ENST00000577031.5 link	c.292-576G>T		intron_variant	Intron 4 of 4	4		ENSP00000459113.1	I3L1U7

Frequencies

GnomAD3 genomes

AF:

0.00817

AC:

1243

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00656

AC:

1634

AN:

248986

Hom.:

AF XY:

0.00653

AC XY:

883

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.00187

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00560

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00773

GnomAD4 exome

AF:

0.0114

AC:

16600

AN:

1460812

Hom.:

102

Cov.:

AF XY:

0.0108

AC XY:

7869

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.00637

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00816

AC:

1243

AN:

152330

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

593

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00729

Hom.:

Bravo

AF:

0.00791

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.00984

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 03, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GLIS2: BP4, BP7, BS1, BS2 -

not specified

Benign:2

Jan 30, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nephronophthisis

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nephronophthisis 7

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.0

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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