chr12-21536802-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021957.4(GYS2):​c.*152C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 645,728 control chromosomes in the GnomAD database, including 108,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 20348 hom., cov: 32)
Exomes 𝑓: 0.59 ( 87865 hom. )

Consequence

GYS2
NM_021957.4 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 1.15
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]
SPX (HGNC:28139): (spexin hormone) The protein encoded by this gene is a hormone involved in modulation of cardiovascular and renal function. It has also been shown in rats to cause weight loss. Several transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 12-21536802-G-A is Benign according to our data. Variant chr12-21536802-G-A is described in ClinVar as [Benign]. Clinvar id is 307985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GYS2NM_021957.4 linkuse as main transcriptc.*152C>T 3_prime_UTR_variant 16/16 ENST00000261195.3
LOC124902896XR_007063240.1 linkuse as main transcriptn.519-244G>A intron_variant, non_coding_transcript_variant
GYS2XM_006719063.4 linkuse as main transcriptc.*152C>T 3_prime_UTR_variant 15/15
GYS2XM_024448960.2 linkuse as main transcriptc.*42+110C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GYS2ENST00000261195.3 linkuse as main transcriptc.*152C>T 3_prime_UTR_variant 16/161 NM_021957.4 P1
SPXENST00000537527.1 linkuse as main transcriptn.472-244G>A intron_variant, non_coding_transcript_variant 3
SPXENST00000649016.1 linkuse as main transcriptn.529-244G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.483
AC:
73439
AN:
151920
Hom.:
20339
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.201
Gnomad AMI
AF:
0.439
Gnomad AMR
AF:
0.594
Gnomad ASJ
AF:
0.506
Gnomad EAS
AF:
0.736
Gnomad SAS
AF:
0.699
Gnomad FIN
AF:
0.578
Gnomad MID
AF:
0.351
Gnomad NFE
AF:
0.582
Gnomad OTH
AF:
0.467
GnomAD4 exome
AF:
0.588
AC:
290422
AN:
493690
Hom.:
87865
Cov.:
5
AF XY:
0.592
AC XY:
155704
AN XY:
262802
show subpopulations
Gnomad4 AFR exome
AF:
0.191
Gnomad4 AMR exome
AF:
0.657
Gnomad4 ASJ exome
AF:
0.506
Gnomad4 EAS exome
AF:
0.782
Gnomad4 SAS exome
AF:
0.677
Gnomad4 FIN exome
AF:
0.574
Gnomad4 NFE exome
AF:
0.577
Gnomad4 OTH exome
AF:
0.548
GnomAD4 genome
AF:
0.483
AC:
73469
AN:
152038
Hom.:
20348
Cov.:
32
AF XY:
0.491
AC XY:
36495
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.201
Gnomad4 AMR
AF:
0.595
Gnomad4 ASJ
AF:
0.506
Gnomad4 EAS
AF:
0.735
Gnomad4 SAS
AF:
0.697
Gnomad4 FIN
AF:
0.578
Gnomad4 NFE
AF:
0.582
Gnomad4 OTH
AF:
0.470
Alfa
AF:
0.557
Hom.:
22662
Bravo
AF:
0.471
Asia WGS
AF:
0.661
AC:
2291
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJun 29, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Glycogen storage disorder due to hepatic glycogen synthase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.3
DANN
Benign
0.22

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.

Other links and lift over

dbSNP: rs936; hg19: chr12-21689736; API