Variant 1-213005188-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144567.5(ANGEL2):c.979A>G(p.Met327Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. 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

ANGEL2
NM_144567.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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:

Genome browser will be placed here

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	Protein	UniProt
ANGEL2	NM_144567.5 linkuse as main transcript	c.979A>G	p.Met327Val	missense_variant	5/9	ENST00000366962.8	NP_653168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGEL2	ENST00000366962.8 linkuse as main transcript	c.979A>G	p.Met327Val	missense_variant	5/9	1	NM_144567.5	ENSP00000355929	P1	Q5VTE6-1
ANGEL2	ENST00000360506.6 linkuse as main transcript	c.472A>G	p.Met158Val	missense_variant	4/8	1		ENSP00000353696		Q5VTE6-2
ANGEL2	ENST00000535388.2 linkuse as main transcript	c.472A>G	p.Met158Val	missense_variant	4/8	1		ENSP00000438141		Q5VTE6-2
ANGEL2	ENST00000476904.5 linkuse as main transcript	n.850A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Aug 30, 2021

The c.979A>G (p.M327V) alteration is located in exon 5 (coding exon 5) of the ANGEL2 gene. This alteration results from a A to G substitution at nucleotide position 979, causing the methionine (M) at amino acid position 327 to be replaced by a valine (V). 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

0.099

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.0055

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;.;T

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.83

L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.27

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.024

B;.;.

Vest4

0.65

MutPred

0.44

Loss of stability (P = 0.3203);.;.;

MVP

0.67

MPC

0.36

ClinPred

0.29

GERP RS

4.5

Varity_R

0.23

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over