chr18-745746-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005433.4(YES1):c.686A>G(p.Gln229Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,612,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
YES1
NM_005433.4 missense
NM_005433.4 missense
Scores
3
6
5
Clinical Significance
Conservation
PhyloP100: 5.04
Genes affected
YES1 (HGNC:12841): (YES proto-oncogene 1, Src family tyrosine kinase) This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YES1 | NM_005433.4 | c.686A>G | p.Gln229Arg | missense_variant | 6/12 | ENST00000314574.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YES1 | ENST00000314574.5 | c.686A>G | p.Gln229Arg | missense_variant | 6/12 | 1 | NM_005433.4 | P1 | |
YES1 | ENST00000584307.5 | c.686A>G | p.Gln229Arg | missense_variant | 6/12 | 1 | P1 | ||
YES1 | ENST00000577961.5 | c.701A>G | p.Gln234Arg | missense_variant | 6/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460376Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726438
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
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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 24, 2022 | The c.686A>G (p.Q229R) alteration is located in exon 6 (coding exon 5) of the YES1 gene. This alteration results from a A to G substitution at nucleotide position 686, causing the glutamine (Q) at amino acid position 229 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T
Polyphen
0.016
.;B;B
Vest4
MutPred
0.53
.;Gain of MoRF binding (P = 0.03);Gain of MoRF binding (P = 0.03);
MVP
MPC
0.45
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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