Genetic Variant NM_016201.4:c.2204C>T (chr3-134358620-G-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_016201.4(AMOTL2):c.2204C>T(p.Pro735Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P735R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AMOTL2
NM_016201.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

2 publications found

Variant links:

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]

AMOTL2 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=0.08931133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016201.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMOTL2	NM_016201.4	MANE Select	c.2204C>T	p.Pro735Leu	missense	Exon 9 of 10	NP_057285.3
AMOTL2	NM_001278683.1		c.2375C>T	p.Pro792Leu	missense	Exon 9 of 10	NP_001265612.1	Q9Y2J4-4
AMOTL2	NM_001363943.2		c.2201C>T	p.Pro734Leu	missense	Exon 9 of 10	NP_001350872.1	Q9Y2J4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMOTL2	ENST00000249883.10	TSL:1 MANE Select	c.2204C>T	p.Pro735Leu	missense	Exon 9 of 10	ENSP00000249883.5	Q9Y2J4-2
AMOTL2	ENST00000513145.1	TSL:1	c.2195C>T	p.Pro732Leu	missense	Exon 9 of 10	ENSP00000425475.1	Q9Y2J4-3
AMOTL2	ENST00000514516.5	TSL:2	c.2375C>T	p.Pro792Leu	missense	Exon 9 of 10	ENSP00000424765.1	Q9Y2J4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250858

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000447

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111890

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.016

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.67

M_CAP

Benign

0.0058

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

1.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.0

REVEL

Benign

0.054

Sift

Uncertain

0.016

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.077

MutPred

0.11

Loss of catalytic residue at P734 (P = 0.016)

MVP

0.35

MPC

0.14

ClinPred

0.060

GERP RS

3.6

Varity_R

0.098

gMVP

0.14

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over