rs864321652
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_002025.4(AFF2):c.*4554C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 24)
Consequence
AFF2
NM_002025.4 3_prime_UTR
NM_002025.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.425
Genes affected
AFF2 (HGNC:3776): (ALF transcription elongation factor 2) This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFF2 | NM_002025.4 | c.*4554C>G | 3_prime_UTR_variant | 21/21 | ENST00000370460.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFF2 | ENST00000370460.7 | c.*4554C>G | 3_prime_UTR_variant | 21/21 | 5 | NM_002025.4 | P1 | ||
AFF2 | ENST00000286437.7 | c.*4554C>G | 3_prime_UTR_variant | 18/18 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FRAXE Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Strand Center for Genomics and Personalized Medicine, Strand Life Sciences Pvt Ltd | - | Though this variant has not been reported in a clinical context, 2 other variants in the 3'UTR of AFF2, *3206C>T and *2338T>C, have been reported in males with autism. The variants were shown to alter AFF2 gene expression levels in a tissue specific manner [PMID:22773736]. Both silencing and overexpression have been implicated in ASD susceptibility [PMID:22773736], [PMID:23562910]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at