rs567418545

Variant names:

• chr1-212995175-C-T
• rs567418545
• NM_144567.5:c.1501G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_144567.5(ANGEL2):​c.1501G>A​(p.Val501Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,604,908 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000041 (2 hom.)
• Consequence: ANGEL2 NM_144567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032823175).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGEL2	NM_144567.5	MANE Select	c.1501G>A	p.Val501Ile	missense	Exon 9 of 9	NP_653168.2
	ANGEL2	NM_001300753.2		c.1123G>A	p.Val375Ile	missense	Exon 9 of 9	NP_001287682.1
	ANGEL2	NM_001300755.2		c.1123G>A	p.Val375Ile	missense	Exon 9 of 9	NP_001287684.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGEL2	ENST00000366962.8	TSL:1 MANE Select	c.1501G>A	p.Val501Ile	missense	Exon 9 of 9	ENSP00000355929.3	Q5VTE6-1
	ANGEL2	ENST00000360506.6	TSL:1	c.994G>A	p.Val332Ile	missense	Exon 8 of 8	ENSP00000353696.2	Q5VTE6-2
	ANGEL2	ENST00000535388.2	TSL:1	c.994G>A	p.Val332Ile	missense	Exon 8 of 8	ENSP00000438141.2	Q5VTE6-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000977 AC: 24 AN: 245676 AF XY: 0.000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000413 AC: 60 AN: 1452588 Hom.: 2 Cov.: 30 AF XY: 0.0000526 AC XY: 38 AN XY: 722552

African (AFR) AF: 0.00 AC: 0 AN: 33156

American (AMR) AF: 0.00 AC: 0 AN: 43408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25802

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.000616 AC: 52 AN: 84418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53166

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5722

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107492

Other (OTH) AF: 0.000100 AC: 6 AN: 59936

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.042
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.033	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.29	N
PhyloP100		2.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		0.0040	B
Vest4		0.022
MutPred		0.41		Gain of catalytic residue at L506 (P = 0.079)
MVP		0.69
MPC		0.19
ClinPred		0.071	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.037
gMVP		0.38
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs567418545; hg19: chr1-213168517;