rs797045219

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002025.4(AFF2):​c.292C>A​(p.Pro98Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P98P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Consequence

AFF2
NM_002025.4 missense

Scores

10
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AFF2NM_002025.4 linkuse as main transcriptc.292C>A p.Pro98Thr missense_variant 3/21 ENST00000370460.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFF2ENST00000370460.7 linkuse as main transcriptc.292C>A p.Pro98Thr missense_variant 3/215 NM_002025.4 P1P51816-1
AFF2ENST00000342251.7 linkuse as main transcriptc.280C>A p.Pro94Thr missense_variant 3/201 P51816-3
AFF2ENST00000370457.9 linkuse as main transcriptc.292C>A p.Pro98Thr missense_variant 3/201 P51816-6
AFF2ENST00000370458.5 linkuse as main transcriptc.280C>A p.Pro94Thr missense_variant 3/81 P51816-4

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoSep 11, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.85
D;.;.;.
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Pathogenic
0.92
D
MetaRNN
Pathogenic
0.90
D;D;D;D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Pathogenic
2.9
M;.;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-6.2
D;D;D;.
REVEL
Pathogenic
0.82
Sift
Uncertain
0.0020
D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.69
MutPred
0.75
Loss of loop (P = 0.1258);.;.;Loss of loop (P = 0.1258);
MVP
0.84
MPC
0.64
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.81
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs797045219; hg19: chrX-147743540; API