3-134359385-C-A

Variant names:

• chr3-134359385-C-A
• NM_016201.4:c.2002G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016201.4(AMOTL2):​c.2002G>T​(p.Val668Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,870 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AMOTL2 NM_016201.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31

Genes affected

AMOTL2 (HGNC:17812): (angiomotin like 2) Angiomotin is a protein that binds angiostatin, a circulating inhibitor of the formation of new blood vessels (angiogenesis). Angiomotin mediates angiostatin inhibition of endothelial cell migration and tube formation in vitro. The protein encoded by this gene is related to angiomotin and is a member of the motin protein family. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

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=0.24001169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOTL2	NM_016201.4	c.2002G>T	p.Val668Leu	missense_variant	Exon 8 of 10	ENST00000249883.10	NP_057285.3
AMOTL2	NM_001278683.1	c.2176G>T	p.Val726Leu	missense_variant	Exon 8 of 10		NP_001265612.1
AMOTL2	NM_001363943.2	c.2002G>T	p.Val668Leu	missense_variant	Exon 8 of 10		NP_001350872.1
AMOTL2	NM_001278685.2	c.1996G>T	p.Val666Leu	missense_variant	Exon 8 of 10		NP_001265614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMOTL2	ENST00000249883.10	c.2002G>T	p.Val668Leu	missense_variant	Exon 8 of 10	1	NM_016201.4	ENSP00000249883.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2002G>T (p.V668L) alteration is located in exon 8 (coding exon 7) of the AMOTL2 gene. This alteration results from a G to T substitution at nucleotide position 2002, causing the valine (V) at amino acid position 668 to be replaced by a leucine (L). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	.;T;.;.
Eigen	Benign	0.085
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.46	T;T;T;T
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.49	P;.;.;P
Vest4		0.42
MutPred		0.26		Loss of MoRF binding (P = 0.0982);Loss of MoRF binding (P = 0.0982);.;.;
MVP		0.28
MPC		0.60
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-134078227;