dbSNP rs2050260648: ATXN2L:p.Pro17Thr (chr16-28823308-C-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_007245.4(ATXN2L):c.49C>A(p.Pro17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,339,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P17S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ATXN2L
NM_007245.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.78

Publications

0 publications found

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:

ENSG00000275807 (HGNC:):

ENSG00000275807 links:

Genome browser will be placed here

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=0.2337232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN2L	NM_007245.4	MANE Select	c.49C>A	p.Pro17Thr	missense	Exon 1 of 22	NP_009176.2
ATXN2L	NM_001387166.1		c.49C>A	p.Pro17Thr	missense	Exon 1 of 24	NP_001374095.1
ATXN2L	NM_001387167.1		c.49C>A	p.Pro17Thr	missense	Exon 1 of 24	NP_001374096.1	Q8WWM7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN2L	ENST00000336783.9	TSL:1 MANE Select	c.49C>A	p.Pro17Thr	missense	Exon 1 of 22	ENSP00000338718.4	Q8WWM7-1
ATXN2L	ENST00000395547.6	TSL:1	c.49C>A	p.Pro17Thr	missense	Exon 1 of 24	ENSP00000378917.2	Q8WWM7-3
ATXN2L	ENST00000564304.5	TSL:1	c.49C>A	p.Pro17Thr	missense	Exon 1 of 23	ENSP00000457613.1	H3BUF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1339028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665414

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27290

American (AMR)

AF:

0.00

AC:

AN:

29626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22450

East Asian (EAS)

AF:

0.00

AC:

AN:

31340

South Asian (SAS)

AF:

0.00

AC:

AN:

72914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3814

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1053862

Other (OTH)

AF:

0.00

AC:

AN:

54076

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

0.15

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

2.8

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.27

REVEL

Benign

0.067

Sift

Benign

0.061

Sift4G

Benign

0.069

Polyphen

0.84

Vest4

0.32

MutPred

0.23

Gain of phosphorylation at P17 (P = 0.0073)

MVP

0.31

MPC

0.56

ClinPred

0.65

GERP RS

3.9

PromoterAI

0.0079

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.9

Varity_R

0.21

gMVP

0.21

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over