Genetic Variant ATL2:p.Leu503Val (chr2-38298269-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001135673.4(ATL2):c.1507T>G(p.Leu503Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,846 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ATL2
NM_001135673.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

ATL2 (HGNC:24047): (atlastin GTPase 2) Enables identical protein binding activity. Involved in Golgi organization; endoplasmic reticulum tubular network membrane organization; and protein homooligomerization. Located in endoplasmic reticulum tubular network membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38880017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL2	NM_001135673.4 link	c.1507T>G	p.Leu503Val	missense_variant	Exon 12 of 13	ENST00000378954.9	NP_001129145.1	Q8NHH9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL2	ENST00000378954.9 link	c.1507T>G	p.Leu503Val	missense_variant	Exon 12 of 13	1	NM_001135673.4	ENSP00000368237.4		Q8NHH9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1507T>G (p.L503V) alteration is located in exon 12 (coding exon 12) of the ATL2 gene. This alteration results from a T to G substitution at nucleotide position 1507, causing the leucine (L) at amino acid position 503 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

0.075

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;.;.;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.0072

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;.;D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.39

T;T;T;T;T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.9

M;.;.;M;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

N;N;N;N;N;.

REVEL

Uncertain

0.40

Sift

Benign

0.086

T;T;T;T;T;.

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.010

B;B;.;B;.;B

Vest4

0.52

MutPred

0.42

Gain of catalytic residue at L503 (P = 0.1542);.;.;Gain of catalytic residue at L503 (P = 0.1542);.;.;

MVP

0.86

MPC

0.15

ClinPred

0.31

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.052

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over