chr1-28742859-A-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_016258.3(YTHDF2):āc.589A>Gā(p.Thr197Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000638 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000068 ( 0 hom. )
Consequence
YTHDF2
NM_016258.3 missense
NM_016258.3 missense
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 3.81
Genes affected
YTHDF2 (HGNC:31675): (YTH N6-methyladenosine RNA binding protein F2) This gene encodes a member of the YTH (YT521-B homology) superfamily containing YTH domain. The YTH domain is typical for the eukaryotes and is particularly abundant in plants. The YTH domain is usually located in the middle of the protein sequence and may function in binding to RNA. In addition to a YTH domain, this protein has a proline rich region which may be involved in signal transduction. An Alu-rich domain has been identified in one of the introns of this gene, which is thought to be associated with human longevity. In addition, reciprocal translocations between this gene and the Runx1 (AML1) gene on chromosome 21 has been observed in patients with acute myeloid leukemia. This gene was initially mapped to chromosome 14, which was later turned out to be a pseudogene. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Oct 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.04846835).
BS2
High AC in GnomAdExome4 at 99 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YTHDF2 | NM_016258.3 | c.589A>G | p.Thr197Ala | missense_variant | 4/5 | ENST00000373812.8 | |
YTHDF2 | NM_001173128.2 | c.589A>G | p.Thr197Ala | missense_variant | 5/6 | ||
YTHDF2 | NM_001172828.2 | c.439A>G | p.Thr147Ala | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YTHDF2 | ENST00000373812.8 | c.589A>G | p.Thr197Ala | missense_variant | 4/5 | 1 | NM_016258.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249540Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135404
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 46AN XY: 727244
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74328
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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 submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The c.589A>G (p.T197A) alteration is located in exon 4 (coding exon 4) of the YTHDF2 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the threonine (T) at amino acid position 197 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;T;.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.0010
.;B;B;.;.
Vest4
0.39, 0.42, 0.42
MVP
MPC
0.60
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at