Genetic Variant ATXN2L:c.466-46T>C (chr16-28826194-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007245.4(ATXN2L):c.466-46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,601,164 control chromosomes in the GnomAD database, including 125,554 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12781 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112773 hom. )

Consequence

ATXN2L
NM_007245.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.42

Publications

136 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
ATXN2L	NM_007245.4	MANE Select	c.466-46T>C	intron	N/A	NP_009176.2
ATXN2L	NM_001387166.1		c.466-46T>C	intron	N/A	NP_001374095.1
ATXN2L	NM_001387167.1		c.466-46T>C	intron	N/A	NP_001374096.1	Q8WWM7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATXN2L	ENST00000336783.9	TSL:1 MANE Select	c.466-46T>C	intron	N/A	ENSP00000338718.4	Q8WWM7-1
ATXN2L	ENST00000395547.6	TSL:1	c.466-46T>C	intron	N/A	ENSP00000378917.2	Q8WWM7-3
ATXN2L	ENST00000564304.5	TSL:1	c.466-46T>C	intron	N/A	ENSP00000457613.1	H3BUF6

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61270

AN:

151834

Hom.:

12728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.383

AC:

94867

AN:

247802

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.455

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.389

AC:

564238

AN:

1449212

Hom.:

112773

Cov.:

AF XY:

0.384

AC XY:

276006

AN XY:

719052

show subpopulations

African (AFR)

AF:

0.449

AC:

14857

AN:

33102

American (AMR)

AF:

0.505

AC:

21993

AN:

43552

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7038

AN:

25800

East Asian (EAS)

AF:

0.250

AC:

9871

AN:

39420

South Asian (SAS)

AF:

0.232

AC:

19927

AN:

85938

European-Finnish (FIN)

AF:

0.440

AC:

23390

AN:

53206

Middle Eastern (MID)

AF:

0.230

AC:

1275

AN:

5550

European-Non Finnish (NFE)

AF:

0.402

AC:

443565

AN:

1102862

Other (OTH)

AF:

0.373

AC:

22322

AN:

59782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

18034

36068

54102

72136

90170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13742

27484

41226

54968

68710

<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:

0.404

AC:

61387

AN:

151952

Hom.:

12781

Cov.:

AF XY:

0.401

AC XY:

29800

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.449

AC:

18592

AN:

41426

American (AMR)

AF:

0.430

AC:

6568

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

937

AN:

3470

East Asian (EAS)

AF:

0.279

AC:

1443

AN:

5176

South Asian (SAS)

AF:

0.221

AC:

1066

AN:

4818

European-Finnish (FIN)

AF:

0.441

AC:

4648

AN:

10532

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.399

AC:

27097

AN:

67952

Other (OTH)

AF:

0.352

AC:

743

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1829

3657

5486

7314

9143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.389

Hom.:

51804

Bravo

AF:

0.408

Asia WGS

AF:

0.348

AC:

1208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.016

(source)

DANN

Benign

0.28

PhyloP100

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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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