rs75495782
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_032575.3(GLIS2):c.1259C>T(p.Pro420Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,547,636 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_032575.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLIS2 | NM_032575.3 | c.1259C>T | p.Pro420Leu | missense_variant | 7/7 | ENST00000433375.2 | NP_115964.2 | |
GLIS2 | NM_001318918.2 | c.1259C>T | p.Pro420Leu | missense_variant | 8/8 | NP_001305847.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLIS2 | ENST00000433375.2 | c.1259C>T | p.Pro420Leu | missense_variant | 7/7 | 1 | NM_032575.3 | ENSP00000395547.1 | ||
GLIS2 | ENST00000262366.7 | c.1259C>T | p.Pro420Leu | missense_variant | 8/8 | 2 | ENSP00000262366.3 | |||
PAM16 | ENST00000577031.5 | c.291+3712G>A | intron_variant | 4 | ENSP00000459113.1 | |||||
ENSG00000262712 | ENST00000574705.1 | n.611G>A | non_coding_transcript_exon_variant | 1/1 | 6 |
Frequencies
GnomAD3 genomes AF: 0.00842 AC: 1281AN: 152214Hom.: 21 Cov.: 34
GnomAD3 exomes AF: 0.00176 AC: 258AN: 146918Hom.: 3 AF XY: 0.00149 AC XY: 118AN XY: 79070
GnomAD4 exome AF: 0.000972 AC: 1356AN: 1395304Hom.: 19 Cov.: 35 AF XY: 0.000838 AC XY: 577AN XY: 688390
GnomAD4 genome AF: 0.00842 AC: 1282AN: 152332Hom.: 21 Cov.: 34 AF XY: 0.00817 AC XY: 609AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2024 | See Variant Classification Assertion Criteria. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 28, 2021 | - - |
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Nephronophthisis 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at