1-213013281-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144567.5(ANGEL2):āc.197A>Gā(p.Tyr66Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,460,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000012 ( 0 hom. )
Consequence
ANGEL2
NM_144567.5 missense
NM_144567.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 4.26
Genes affected
ANGEL2 (HGNC:30534): (angel homolog 2) Enables mRNA 3'-UTR binding activity. Involved in 3'-UTR-mediated mRNA stabilization and negative regulation of mitotic cell cycle. Located in Cajal body and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25336182).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANGEL2 | NM_144567.5 | c.197A>G | p.Tyr66Cys | missense_variant | 2/9 | ENST00000366962.8 | NP_653168.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANGEL2 | ENST00000366962.8 | c.197A>G | p.Tyr66Cys | missense_variant | 2/9 | 1 | NM_144567.5 | ENSP00000355929 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251490Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135918
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460250Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726422
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GnomAD4 genome Cov.: 33
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33
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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 | May 20, 2024 | The c.197A>G (p.Y66C) alteration is located in exon 2 (coding exon 2) of the ANGEL2 gene. This alteration results from a A to G substitution at nucleotide position 197, causing the tyrosine (Y) at amino acid position 66 to be replaced by a cysteine (C). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.1359);
MVP
MPC
ClinPred
T
GERP RS
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