chr14-50905380-CA-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002863.5(PYGL):c.*11delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10889 hom., cov: 0)

Exomes 𝑓: 0.30 ( 73702 hom. )

Consequence

PYGL
NM_002863.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00

Publications

8 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 -16 ACMG points.

BP6

Variant 14-50905380-CA-C is Benign according to our data. Variant chr14-50905380-CA-C is described in ClinVar as Benign. ClinVar VariationId is 258828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGL	NM_002863.5 link	c.*11delT		3_prime_UTR_variant	Exon 20 of 20	ENST00000216392.8	NP_002854.3
PYGL	NM_001163940.2 link	c.*11delT		3_prime_UTR_variant	Exon 19 of 19		NP_001157412.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PYGL	ENST00000216392.8 link	c.*11delT	3_prime_UTR_variant	Exon 20 of 20	1	NM_002863.5	ENSP00000216392.7
PYGL	ENST00000532462.5 link	c.2379+2890delT	intron_variant	Intron 19 of 19	1		ENSP00000431657.1
PYGL	ENST00000544180.6 link	c.*11delT	3_prime_UTR_variant	Exon 19 of 19	2		ENSP00000443787.1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54825

AN:

151826

Hom.:

10854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.426

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.376

GnomAD2 exomes

AF:

0.371

AC:

93051

AN:

251102

AF XY:

0.357

show subpopulations

Gnomad AFR exome

AF:

0.457

Gnomad AMR exome

AF:

0.622

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.304

AC:

441245

AN:

1449560

Hom.:

73702

Cov.:

AF XY:

0.304

AC XY:

219596

AN XY:

721956

show subpopulations

African (AFR)

AF:

0.469

AC:

15578

AN:

33182

American (AMR)

AF:

0.605

AC:

27039

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

6617

AN:

26040

East Asian (EAS)

AF:

0.627

AC:

24835

AN:

39606

South Asian (SAS)

AF:

0.354

AC:

30407

AN:

85962

European-Finnish (FIN)

AF:

0.301

AC:

16071

AN:

53380

Middle Eastern (MID)

AF:

0.380

AC:

2178

AN:

5734

European-Non Finnish (NFE)

AF:

0.271

AC:

298723

AN:

1101016

Other (OTH)

AF:

0.330

AC:

19797

AN:

59964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

13258

26516

39775

53033

66291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10282

20564

30846

41128

51410

<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:

0.361

AC:

54906

AN:

151944

Hom.:

10889

Cov.:

AF XY:

0.367

AC XY:

27278

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.459

AC:

19016

AN:

41454

American (AMR)

AF:

0.482

AC:

7353

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

837

AN:

3462

East Asian (EAS)

AF:

0.607

AC:

3133

AN:

5158

South Asian (SAS)

AF:

0.366

AC:

1760

AN:

4814

European-Finnish (FIN)

AF:

0.304

AC:

3202

AN:

10532

Middle Eastern (MID)

AF:

0.428

AC:

124

AN:

290

European-Non Finnish (NFE)

AF:

0.273

AC:

18582

AN:

67954

Other (OTH)

AF:

0.376

AC:

794

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1699

3398

5098

6797

8496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.309

Hom.:

1394

Bravo

AF:

0.384

Asia WGS

AF:

0.489

AC:

1699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 10, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 26, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease, type VI

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over