rs2227891

Variant names:

• chr20-25282133-G-A
• rs2227891
• NM_002862.4:c.1504G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002862.4(PYGB):​c.1504G>A​(p.Asp502Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,611,656 control chromosomes in the GnomAD database, including 26,114 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2156 hom., cov: 33)
  • Exomes 𝑓: 0.18 (23958 hom.)
• Consequence: PYGB NM_002862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.98

Genes affected

PYGB (HGNC:9723): (glycogen phosphorylase B) The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013472438).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGB	NM_002862.4	c.1504G>A	p.Asp502Asn	missense_variant	Exon 12 of 20	ENST00000216962.9	NP_002853.2
PYGB	XM_047440342.1	c.1504G>A	p.Asp502Asn	missense_variant	Exon 12 of 16		XP_047296298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.1504G>A	p.Asp502Asn	missense_variant	Exon 12 of 20	1	NM_002862.4	ENSP00000216962.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23774 AN: 152104 Hom.: 2151 Cov.: 33

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.169 AC: 42262 AN: 250324 Hom.: 3988 AF XY: 0.164 AC XY: 22243 AN XY: 135392

Gnomad AFR exome AF: 0.0764

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.0945

Gnomad EAS exome AF: 0.336

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.176 AC: 257201 AN: 1459434 Hom.: 23958 Cov.: 32 AF XY: 0.174 AC XY: 126214 AN XY: 726070

Gnomad4 AFR exome AF: 0.0744

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0928

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.156 AC: 23778 AN: 152222 Hom.: 2156 Cov.: 33 AF XY: 0.157 AC XY: 11652 AN XY: 74416

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.146

Alfa AF: 0.173 Hom.: 2547

Bravo AF: 0.150

TwinsUK AF: 0.194 AC: 720

ALSPAC AF: 0.178 AC: 685

ESP6500AA AF: 0.0793 AC: 349

ESP6500EA AF: 0.185 AC: 1593

ExAC AF: 0.166 AC: 20195

Asia WGS AF: 0.239 AC: 828 AN: 3478

EpiCase AF: 0.175

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.28
Sift	Benign	0.15	T
Sift4G	Benign	0.41	T
Polyphen		0.0090	B
Vest4		0.14
MPC		0.21
ClinPred		0.11	T
GERP RS		3.9
Varity_R		0.30
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs2227891; hg19: chr20-25262769; COSMIC: COSV53816266; COSMIC: COSV53816266;