1-213013281-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144567.5(ANGEL2):ā€‹c.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

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26
Variant links:
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]

Genome browser will be placed here

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
ANGEL2NM_144567.5 linkuse as main transcriptc.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
ANGEL2ENST00000366962.8 linkuse as main transcriptc.197A>G p.Tyr66Cys missense_variant 2/91 NM_144567.5 ENSP00000355929 P1Q5VTE6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251490
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000489
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1460250
Hom.:
0
Cov.:
31
AF XY:
0.00000826
AC XY:
6
AN XY:
726422
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000428
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000151
ExAC
AF:
0.0000247
AC:
3

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 testingAmbry GeneticsMay 20, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.017
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.54
D;D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.17
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.085
T
Polyphen
1.0
D
Vest4
0.50
MutPred
0.18
Gain of disorder (P = 0.1359);
MVP
0.38
MPC
0.85
ClinPred
0.25
T
GERP RS
5.5
Varity_R
0.089
gMVP
0.64

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: rs759667959; hg19: chr1-213186623; API