Variant 12-21559148-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021957.4(GYS2):c.1251C>A(p.Asn417Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GYS2
NM_021957.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

GYS2 (HGNC:4707): (glycogen synthase 2) The protein encoded by this gene, liver glycogen synthase, catalyzes the rate-limiting step in the synthesis of glycogen - the transfer of a glucose molecule from UDP-glucose to a terminal branch of the glycogen molecule. Mutations in this gene cause glycogen storage disease type 0 (GSD-0) - a rare type of early childhood fasting hypoglycemia with decreased liver glycogen content. [provided by RefSeq, Dec 2009]

GYS2 links:

ENSG00000285854 (HGNC:):

ENSG00000285854 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20517996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYS2	NM_021957.4 linkuse as main transcript	c.1251C>A	p.Asn417Lys	missense_variant	10/16	ENST00000261195.3	NP_068776.2	P54840
GYS2	XM_024448960.2 linkuse as main transcript	c.1251C>A	p.Asn417Lys	missense_variant	10/17		XP_024304728.1
GYS2	XM_006719063.4 linkuse as main transcript	c.1020C>A	p.Asn340Lys	missense_variant	9/15		XP_006719126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GYS2	ENST00000261195.3 linkuse as main transcript	c.1251C>A	p.Asn417Lys	missense_variant	10/16	1	NM_021957.4	ENSP00000261195.2	P54840
ENSG00000285854	ENST00000647960.1 linkuse as main transcript	n.*1253C>A		non_coding_transcript_exon_variant	17/23			ENSP00000497202.1	A0A3B3IS95
ENSG00000285854	ENST00000647960.1 linkuse as main transcript	n.*1253C>A		3_prime_UTR_variant	17/23			ENSP00000497202.1	A0A3B3IS95
ENSG00000285854	ENST00000648372.1 linkuse as main transcript	n.1178C>A		non_coding_transcript_exon_variant	10/11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250704

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454782

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000761

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.21

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Benign

0.020

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

REVEL

Benign

0.077

Sift

Benign

0.43

Sift4G

Benign

0.97

Polyphen

0.026

Vest4

0.38

MutPred

0.44

Gain of ubiquitination at N417 (P = 0.0203);

MVP

0.46

MPC

0.18

ClinPred

0.16

GERP RS

0.16

Varity_R

0.046

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over