X-148652129-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002025.4(AFF2):c.178T>C(p.Tyr60His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,186,144 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y60C) has been classified as Likely benign.
Frequency
Consequence
NM_002025.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFF2 | NM_002025.4 | c.178T>C | p.Tyr60His | missense_variant, splice_region_variant | 2/21 | ENST00000370460.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFF2 | ENST00000370460.7 | c.178T>C | p.Tyr60His | missense_variant, splice_region_variant | 2/21 | 5 | NM_002025.4 | P1 | |
AFF2 | ENST00000370457.9 | c.178T>C | p.Tyr60His | missense_variant, splice_region_variant | 2/20 | 1 | |||
AFF2 | ENST00000342251.7 | c.168+10T>C | intron_variant | 1 | |||||
AFF2 | ENST00000370458.5 | c.168+10T>C | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111867Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34035
GnomAD4 exome AF: 0.0000140 AC: 15AN: 1074277Hom.: 0 Cov.: 25 AF XY: 0.0000175 AC XY: 6AN XY: 343123
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111867Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34035
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2019 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at