Genetic Variant ATL2:p.Arg322Gln (chr2-38309485-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001135673.4(ATL2):c.965G>A(p.Arg322Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,611,176 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 43 hom. )

Consequence

ATL2
NM_001135673.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056197047).

BP6

Variant 2-38309485-C-T is Benign according to our data. Variant chr2-38309485-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650839.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 806 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL2	NM_001135673.4 link	c.965G>A	p.Arg322Gln	missense_variant	Exon 9 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.965G>A	p.Arg322Gln	missense_variant	Exon 9 of 13	1	NM_001135673.4	ENSP00000368237.4		Q8NHH9-1

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

805

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0355

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00534

AC:

1330

AN:

248970

Hom.:

AF XY:

0.00534

AC XY:

720

AN XY:

134800

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000329

Gnomad FIN exome

AF:

0.0291

Gnomad NFE exome

AF:

0.00569

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00497

AC:

7251

AN:

1459130

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

3551

AN XY:

725996

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.000542

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000361

Gnomad4 FIN exome

AF:

0.0282

Gnomad4 NFE exome

AF:

0.00487

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.00530

AC:

806

AN:

152046

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

463

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000699

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0355

Gnomad4 NFE

AF:

0.00537

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00284

ExAC

AF:

0.00521

AC:

633

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATL2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;T;.;.;.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.93

D;.;D;D;D;D;D

MetaRNN

Benign

0.0056

T;T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.63

N;.;.;N;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.60

N;N;N;N;N;.;N

REVEL

Benign

0.17

Sift

Benign

0.24

T;T;T;T;T;.;T

Sift4G

Benign

0.41

T;T;T;T;T;T;T

Polyphen

0.0010

B;B;.;B;.;B;.

Vest4

0.18

MVP

0.52

MPC

0.16

ClinPred

0.0099

GERP RS

3.1

Varity_R

0.042

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over