1-212995184-C-T

Variant names:

• chr1-212995184-C-T
• rs972543902
• NM_144567.5:c.1492G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144567.5(ANGEL2):​c.1492G>A​(p.Val498Ile) 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. 16/22 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)
• Consequence: ANGEL2 NM_144567.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 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: 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=0.0847311).

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.1492G>A	p.Val498Ile	missense	Exon 9 of 9	NP_653168.2
	ANGEL2	NM_001300753.2		c.1114G>A	p.Val372Ile	missense	Exon 9 of 9	NP_001287682.1
	ANGEL2	NM_001300755.2		c.1114G>A	p.Val372Ile	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.1492G>A	p.Val498Ile	missense	Exon 9 of 9	ENSP00000355929.3	Q5VTE6-1
	ANGEL2	ENST00000360506.6	TSL:1	c.985G>A	p.Val329Ile	missense	Exon 8 of 8	ENSP00000353696.2	Q5VTE6-2
	ANGEL2	ENST00000535388.2	TSL:1	c.985G>A	p.Val329Ile	missense	Exon 8 of 8	ENSP00000438141.2	Q5VTE6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.085	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.15
Sift	Benign	0.41	T
Sift4G	Benign	0.44	T
Polyphen		0.20	B
Vest4		0.067
MutPred		0.41		Loss of loop (P = 0.1242)
MVP		0.67
MPC		0.21
ClinPred		0.31	T
GERP RS		4.8
Varity_R		0.034
gMVP		0.38
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs972543902; hg19: chr1-213168526;