rs112926217
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032575.3(GLIS2):c.894C>T(p.Pro298=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,612,590 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0073 ( 19 hom., cov: 34)
Exomes 𝑓: 0.00077 ( 17 hom. )
Consequence
GLIS2
NM_032575.3 synonymous
NM_032575.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.55
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 16-4336843-C-T is Benign according to our data. Variant chr16-4336843-C-T is described in ClinVar as [Benign]. Clinvar id is 96225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.55 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00728 (1109/152260) while in subpopulation AFR AF= 0.0251 (1043/41550). AF 95% confidence interval is 0.0238. There are 19 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 19 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLIS2 | NM_032575.3 | c.894C>T | p.Pro298= | synonymous_variant | 7/7 | ENST00000433375.2 | |
GLIS2 | NM_001318918.2 | c.894C>T | p.Pro298= | synonymous_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLIS2 | ENST00000433375.2 | c.894C>T | p.Pro298= | synonymous_variant | 7/7 | 1 | NM_032575.3 | P1 | |
ENST00000574705.1 | n.976G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
GLIS2 | ENST00000262366.7 | c.894C>T | p.Pro298= | synonymous_variant | 8/8 | 2 | P1 | ||
PAM16 | ENST00000577031.5 | c.291+4077G>A | intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00729 AC: 1109AN: 152142Hom.: 19 Cov.: 34
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GnomAD3 exomes AF: 0.00195 AC: 488AN: 249640Hom.: 9 AF XY: 0.00140 AC XY: 190AN XY: 135536
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GnomAD4 exome AF: 0.000772 AC: 1128AN: 1460330Hom.: 17 Cov.: 35 AF XY: 0.000691 AC XY: 502AN XY: 726480
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GnomAD4 genome ? AF: 0.00728 AC: 1109AN: 152260Hom.: 19 Cov.: 34 AF XY: 0.00712 AC XY: 530AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 05, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 13, 2022 | - - |
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Nephronophthisis 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at