Variant 16-28823369-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000336783.9(ATXN2L):c.110G>A(p.Gly37Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,344,200 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: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

ATXN2L
ENST00000336783.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.126

Variant links:

Genes affected

ATXN2L (HGNC:31326): (ataxin 2 like) This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATXN2L links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06470668).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN2L	NM_007245.4 linkuse as main transcript	c.110G>A	p.Gly37Asp	missense_variant	1/22	ENST00000336783.9	NP_009176.2
LOC124903672	XR_007065042.1 linkuse as main transcript	n.149+525C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN2L	ENST00000336783.9 linkuse as main transcript	c.110G>A	p.Gly37Asp	missense_variant	1/22	1	NM_007245.4	ENSP00000338718	A2	Q8WWM7-1
	ENST00000614819.1 linkuse as main transcript	n.601C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000775

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000719

AC:

AN:

69542

Hom.:

AF XY:

0.0000991

AC XY:

AN XY:

40354

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000542

Gnomad SAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000545

AC:

AN:

1192130

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

579264

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00144

Gnomad4 SAS exome

AF:

0.0000710

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000142

Gnomad4 OTH exome

AF:

0.000105

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000778

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000473

AC:

Asia WGS

AF:

0.00203

AC:

AN:

3462

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.110G>A (p.G37D) alteration is located in exon 1 (coding exon 1) of the ATXN2L gene. This alteration results from a G to A substitution at nucleotide position 110, causing the glycine (G) at amino acid position 37 to be replaced by an aspartic acid (D). 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

0.28

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

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

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.88

D;D;D;D;D;D;D

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.065

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

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

MutationTaster

Benign

0.97

N;N;N;N;N;N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.40

N;N;N;N;N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.0030

D;D;D;D;D;D;D

Sift4G

Benign

0.11

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

Polyphen

0.12

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

Vest4

0.24

MutPred

0.087

Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);

MVP

0.36

MPC

1.6

ClinPred

0.17

GERP RS

3.0

Varity_R

0.18

gMVP

0.30

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