rs2275466

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002863.5(PYGL):c.2380-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,595,938 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 91 hom., cov: 33)

Exomes 𝑓: 0.024 ( 604 hom. )

Consequence

PYGL
NM_002863.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.137

Publications

2 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics

PYGL links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002863.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-50905597-C-T is Benign according to our data. Variant chr14-50905597-C-T is described in ClinVar as Benign. ClinVar VariationId is 258839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002863.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGL	NM_002863.5	MANE Select	c.2380-41G>A		intron	N/A	NP_002854.3
	PYGL	NM_001163940.2		c.2278-41G>A		intron	N/A	NP_001157412.1	P06737-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PYGL	ENST00000216392.8	TSL:1 MANE Select	c.2380-41G>A	intron	N/A	ENSP00000216392.7	P06737-1
PYGL	ENST00000532462.5	TSL:1	c.2379+2674G>A	intron	N/A	ENSP00000431657.1	E9PK47
PYGL	ENST00000874287.1		c.2395-41G>A	intron	N/A	ENSP00000544346.1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4677

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0498

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.0642

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0309

AC:

7749

AN:

250550

AF XY:

0.0296

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.0620

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0265

GnomAD4 exome

AF:

0.0237

AC:

34159

AN:

1443690

Hom.:

604

Cov.:

AF XY:

0.0237

AC XY:

17063

AN XY:

719568

show subpopulations

African (AFR)

AF:

0.0447

AC:

1475

AN:

33020

American (AMR)

AF:

0.0584

AC:

2610

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

374

AN:

26014

East Asian (EAS)

AF:

0.0774

AC:

3063

AN:

39574

South Asian (SAS)

AF:

0.0338

AC:

2903

AN:

85862

European-Finnish (FIN)

AF:

0.0247

AC:

1319

AN:

53360

Middle Eastern (MID)

AF:

0.0129

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0189

AC:

20737

AN:

1095668

Other (OTH)

AF:

0.0268

AC:

1604

AN:

59762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1681

3363

5044

6726

8407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.0308

AC:

4686

AN:

152248

Hom.:

Cov.:

AF XY:

0.0321

AC XY:

2393

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0443

AC:

1839

AN:

41520

American (AMR)

AF:

0.0497

AC:

760

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.0641

AC:

333

AN:

5192

South Asian (SAS)

AF:

0.0332

AC:

160

AN:

4820

European-Finnish (FIN)

AF:

0.0209

AC:

222

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0186

AC:

1266

AN:

68020

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

237

474

710

947

1184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0211

Hom.:

Bravo

AF:

0.0334

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.2

(source)

DANN

Benign

0.37

PhyloP100

0.14

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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