Genetic Variant ANGEL2:p.Val498Phe (chr1-212995184-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144567.5(ANGEL2):c.1492G>T(p.Val498Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V498L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANGEL2
NM_144567.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Publications

0 publications found

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]

ANGEL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07212815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ANGEL2	NM_144567.5	MANE Select	c.1492G>T	p.Val498Phe	missense	Exon 9 of 9	NP_653168.2
ANGEL2	NM_001300753.2		c.1114G>T	p.Val372Phe	missense	Exon 9 of 9	NP_001287682.1
ANGEL2	NM_001300755.2		c.1114G>T	p.Val372Phe	missense	Exon 9 of 9	NP_001287684.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANGEL2	ENST00000366962.8	TSL:1 MANE Select	c.1492G>T	p.Val498Phe	missense	Exon 9 of 9	ENSP00000355929.3	Q5VTE6-1
ANGEL2	ENST00000360506.6	TSL:1	c.985G>T	p.Val329Phe	missense	Exon 8 of 8	ENSP00000353696.2	Q5VTE6-2
ANGEL2	ENST00000535388.2	TSL:1	c.985G>T	p.Val329Phe	missense	Exon 8 of 8	ENSP00000438141.2	Q5VTE6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448406

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720392

African (AFR)

AF:

0.00

AC:

AN:

32938

American (AMR)

AF:

0.00

AC:

AN:

42432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25648

East Asian (EAS)

AF:

0.00

AC:

AN:

39434

South Asian (SAS)

AF:

0.00

AC:

AN:

83512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105878

Other (OTH)

AF:

0.00

AC:

AN:

59778

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.13

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.85

M_CAP

Benign

0.049

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.2

PhyloP100

2.3

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.30

REVEL

Benign

0.17

Sift

Benign

0.72

Sift4G

Benign

0.71

Polyphen

0.016

Vest4

0.16

MutPred

0.55

Loss of loop (P = 0.1242)

MVP

0.54

MPC

0.29

ClinPred

0.42

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.083

gMVP

0.66

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over