Genetic Variant NM_007245.4:c.52C>A (chr16-28823311-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007245.4(ATXN2L):c.52C>A(p.Pro18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000965 in 1,492,436 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

ATXN2L
NM_007245.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.812

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02639398).

BS2

High AC in GnomAd4 at 70 AD gene.

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.52C>A	p.Pro18Thr	missense	Exon 1 of 22	NP_009176.2
ATXN2L	NM_001387166.1		c.52C>A	p.Pro18Thr	missense	Exon 1 of 24	NP_001374095.1
ATXN2L	NM_001387167.1		c.52C>A	p.Pro18Thr	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.52C>A	p.Pro18Thr	missense	Exon 1 of 22	ENSP00000338718.4	Q8WWM7-1
ATXN2L	ENST00000395547.6	TSL:1	c.52C>A	p.Pro18Thr	missense	Exon 1 of 24	ENSP00000378917.2	Q8WWM7-3
ATXN2L	ENST00000564304.5	TSL:1	c.52C>A	p.Pro18Thr	missense	Exon 1 of 23	ENSP00000457613.1	H3BUF6

Frequencies

GnomAD3 genomes

AF:

0.000461

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000115

AC:

AN:

147230

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00150

Gnomad AMR exome

AF:

0.0000514

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000648

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000145

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000552

AC:

AN:

1340364

Hom.:

Cov.:

AF XY:

0.0000570

AC XY:

AN XY:

666124

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

27298

American (AMR)

AF:

0.0000676

AC:

AN:

29594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22458

East Asian (EAS)

AF:

0.0000955

AC:

AN:

31412

South Asian (SAS)

AF:

0.0000273

AC:

AN:

73130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3808

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1054852

Other (OTH)

AF:

0.000111

AC:

AN:

54124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000460

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41530

American (AMR)

AF:

0.000393

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67940

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000582

ESP6500AA

AF:

0.000863

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000170

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.048

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.81

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.30

REVEL

Benign

0.052

Sift

Pathogenic

0.0

Sift4G

Benign

0.098

Polyphen

0.21

Vest4

0.24

MVP

0.29

MPC

0.56

ClinPred

0.20

GERP RS

2.8

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.26

gMVP

0.21

Mutation Taster

=90/10

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over