rs142250604

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_013444.4(UBQLN2):c.1383G>A(p.Gly461Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,210,925 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,407 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., 127 hem., cov: 23)

Exomes 𝑓: 0.0036 ( 7 hom. 1280 hem. )

Consequence

UBQLN2
NM_013444.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.194

Publications

1 publications found

Variant links:

Genes affected

UBQLN2 (HGNC:12509): (ubiquilin 2) This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases; and thus, are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein. [provided by RefSeq, Oct 2009]

UBQLN2 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 15
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

UBQLN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant X-56565256-G-A is Benign according to our data. Variant chrX-56565256-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 368609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.194 with no splicing effect.

BS2

High AC in GnomAd4 at 352 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013444.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN2	NM_013444.4	MANE Select	c.1383G>A	p.Gly461Gly	synonymous	Exon 1 of 1	NP_038472.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN2	ENST00000338222.7	TSL:6 MANE Select	c.1383G>A	p.Gly461Gly	synonymous	Exon 1 of 1	ENSP00000345195.5

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

352

AN:

112734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00306

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000712

Gnomad FIN

AF:

0.0195

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00329

GnomAD2 exomes

AF:

0.00367

AC:

673

AN:

183302

AF XY:

0.00382

show subpopulations

Gnomad AFR exome

AF:

0.000533

Gnomad AMR exome

AF:

0.000912

Gnomad ASJ exome

AF:

0.00240

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00356

AC:

3911

AN:

1098137

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

1280

AN XY:

363497

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

26402

American (AMR)

AF:

0.00145

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00157

AC:

AN:

54137

European-Finnish (FIN)

AF:

0.0171

AC:

691

AN:

40517

Middle Eastern (MID)

AF:

0.00387

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00341

AC:

2875

AN:

842064

Other (OTH)

AF:

0.00323

AC:

149

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

177

355

532

710

887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00312

AC:

352

AN:

112788

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

127

AN XY:

34950

show subpopulations

African (AFR)

AF:

0.000579

AC:

AN:

31107

American (AMR)

AF:

0.00306

AC:

AN:

10790

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.000714

AC:

AN:

2802

European-Finnish (FIN)

AF:

0.0195

AC:

121

AN:

6201

Middle Eastern (MID)

AF:

0.00913

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00310

AC:

165

AN:

53236

Other (OTH)

AF:

0.00325

AC:

AN:

1539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00284

Hom.:

Bravo

AF:

0.00238

EpiCase

AF:

0.00485

EpiControl

AF:

0.00421

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 15

Benign:3

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Oct 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

May 22, 2020

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.7

(source)

DANN

Benign

0.60

PhyloP100

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over