rs2075643

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002863.5(PYGL):c.1020C>T(p.Asp340Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.192 in 1,612,936 control chromosomes in the GnomAD database, including 34,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2974 hom., cov: 33)

Exomes 𝑓: 0.19 ( 31616 hom. )

Consequence

PYGL
NM_002863.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.97

Publications

20 publications found

Variant links:

Genes affected

PYGL (HGNC:9725): (glycogen phosphorylase L) This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2011]

PYGL Gene-Disease associations (from GenCC):

glycogen storage disease VI
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet, Ambry Genetics

PYGL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 14-50916714-G-A is Benign according to our data. Variant chr14-50916714-G-A is described in ClinVar as Benign. ClinVar VariationId is 258830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGL	NM_002863.5 link	c.1020C>T	p.Asp340Asp	synonymous_variant	Exon 9 of 20	ENST00000216392.8	NP_002854.3	P06737-1
PYGL	NM_001163940.2 link	c.918C>T	p.Asp306Asp	synonymous_variant	Exon 8 of 19		NP_001157412.1	P06737-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYGL	ENST00000216392.8 link	c.1020C>T	p.Asp340Asp	synonymous_variant	Exon 9 of 20	1	NM_002863.5	ENSP00000216392.7	P06737-1
PYGL	ENST00000532462.5 link	c.1020C>T	p.Asp340Asp	synonymous_variant	Exon 9 of 20	1		ENSP00000431657.1	E9PK47
PYGL	ENST00000544180.6 link	c.918C>T	p.Asp306Asp	synonymous_variant	Exon 8 of 19	2		ENSP00000443787.1	P06737-2

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26238

AN:

152098

Hom.:

2968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.202

GnomAD2 exomes

AF:

0.239

AC:

60106

AN:

251412

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.0652

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.195

AC:

284209

AN:

1460720

Hom.:

31616

Cov.:

AF XY:

0.194

AC XY:

141273

AN XY:

726756

show subpopulations

African (AFR)

AF:

0.0638

AC:

2137

AN:

33470

American (AMR)

AF:

0.458

AC:

20481

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4375

AN:

26134

East Asian (EAS)

AF:

0.424

AC:

16810

AN:

39690

South Asian (SAS)

AF:

0.220

AC:

18946

AN:

86220

European-Finnish (FIN)

AF:

0.199

AC:

10608

AN:

53416

Middle Eastern (MID)

AF:

0.265

AC:

1521

AN:

5748

European-Non Finnish (NFE)

AF:

0.177

AC:

196995

AN:

1110990

Other (OTH)

AF:

0.204

AC:

12336

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

12379

24758

37137

49516

61895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7170

14340

21510

28680

35850

<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:

0.173

AC:

26259

AN:

152216

Hom.:

2974

Cov.:

AF XY:

0.178

AC XY:

13272

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0646

AC:

2685

AN:

41552

American (AMR)

AF:

0.315

AC:

4820

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

553

AN:

3470

East Asian (EAS)

AF:

0.442

AC:

2287

AN:

5176

South Asian (SAS)

AF:

0.240

AC:

1155

AN:

4822

European-Finnish (FIN)

AF:

0.196

AC:

2075

AN:

10588

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12091

AN:

68000

Other (OTH)

AF:

0.204

AC:

432

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1047

2093

3140

4186

5233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.185

Hom.:

4612

Bravo

AF:

0.183

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.187

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease, type VI

Benign:3

Feb 03, 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. -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.6

(source)

DANN

Benign

0.81

PhyloP100

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over