rs28449480
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_032575.3(GLIS2):c.-11G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,610,762 control chromosomes in the GnomAD database, including 1,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.052 ( 681 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 625 hom. )
Consequence
GLIS2
NM_032575.3 5_prime_UTR
NM_032575.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.508
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 16-4332270-G-A is Benign according to our data. Variant chr16-4332270-G-A is described in ClinVar as [Benign]. Clinvar id is 262084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLIS2 | NM_032575.3 | c.-11G>A | 5_prime_UTR_variant | 2/7 | ENST00000433375.2 | ||
GLIS2 | NM_001318918.2 | c.-11G>A | 5_prime_UTR_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLIS2 | ENST00000433375.2 | c.-11G>A | 5_prime_UTR_variant | 2/7 | 1 | NM_032575.3 | P1 | ||
GLIS2 | ENST00000262366.7 | c.-11G>A | 5_prime_UTR_variant | 3/8 | 2 | P1 | |||
PAM16 | ENST00000577031.5 | c.292-496C>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0521 AC: 7924AN: 152050Hom.: 681 Cov.: 32
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GnomAD3 exomes AF: 0.0142 AC: 3461AN: 243058Hom.: 273 AF XY: 0.0107 AC XY: 1418AN XY: 132322
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GnomAD4 exome AF: 0.00591 AC: 8623AN: 1458596Hom.: 625 Cov.: 32 AF XY: 0.00530 AC XY: 3844AN XY: 725422
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GnomAD4 genome ? AF: 0.0522 AC: 7940AN: 152166Hom.: 681 Cov.: 32 AF XY: 0.0508 AC XY: 3784AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
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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BayesDel_noAF
Benign
CADD
Benign
DANN
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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