rs769481947
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_001012759.3(CTU2):c.873G>A(p.Thr291=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,423,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_001012759.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTU2 | NM_001012759.3 | c.873G>A | p.Thr291= | splice_region_variant, synonymous_variant | 8/15 | ENST00000453996.7 | |
CTU2 | NM_001318507.2 | c.1086G>A | p.Thr362= | splice_region_variant, synonymous_variant | 8/15 | ||
CTU2 | NM_001012762.3 | c.873G>A | p.Thr291= | splice_region_variant, synonymous_variant | 8/14 | ||
CTU2 | NM_001318513.2 | c.612G>A | p.Thr204= | splice_region_variant, synonymous_variant | 7/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTU2 | ENST00000453996.7 | c.873G>A | p.Thr291= | splice_region_variant, synonymous_variant | 8/15 | 1 | NM_001012759.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 26
GnomAD3 exomes AF: 0.00000929 AC: 2AN: 215286Hom.: 0 AF XY: 0.00000848 AC XY: 1AN XY: 117984
GnomAD4 exome AF: 0.0000112 AC: 16AN: 1423670Hom.: 0 Cov.: 37 AF XY: 0.00000565 AC XY: 4AN XY: 707396
GnomAD4 genome ? Cov.: 26
ClinVar
Submissions by phenotype
Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 03, 2020 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | Synonymous variant: previously reported to alter splicing and result in a loss of normal protein fucnction through nonsense-mediated decay (NMD) or protein truncation (PMID: 26633546, PVS1_VS). The variant was co-segregated with Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome in multiple affected family members (PMID: 27480277, PP1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000009, PM2_M). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 27480277, 26633546, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 14, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 05, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at