Variant 16-28823483-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000336783.9(ATXN2L):c.224G>A(p.Gly75Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000819 in 1,221,114 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: 8.2e-7 ( 0 hom. )

Consequence

ATXN2L
ENST00000336783.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

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:

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ACMG classification

Classification made for transcript

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=0.15476513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN2L	NM_007245.4 linkuse as main transcript	c.224G>A	p.Gly75Asp	missense_variant	1/22	ENST00000336783.9	NP_009176.2
LOC124903672	XR_007065042.1 linkuse as main transcript	n.149+411C>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.224G>A	p.Gly75Asp	missense_variant	1/22	1	NM_007245.4	ENSP00000338718	A2	Q8WWM7-1
	ENST00000614819.1 linkuse as main transcript	n.487C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.19e-7

AC:

AN:

1221114

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

597176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 10, 2022

The c.224G>A (p.G75D) 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 224, causing the glycine (G) at amino acid position 75 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

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

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

Eigen

Benign

-0.10

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

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

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.15

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

0.91

PROVEAN

Benign

-0.89

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

REVEL

Benign

0.025

Sift

Benign

0.035

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

Sift4G

Uncertain

0.059

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

Polyphen

0.20

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

Vest4

0.23

MutPred

0.24

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MVP

0.29

MPC

0.67

ClinPred

0.55

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.084

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