X-2843032-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003918.3(GYG2):​c.42C>G​(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 502,712 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 4 hem., cov: 22)
Exomes 𝑓: 0.000038 ( 0 hom. 3 hem. )

Consequence

GYG2
NM_003918.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.608
Variant links:
Genes affected
GYG2 (HGNC:4700): (glycogenin 2) This gene encodes a member of the the glycogenin family. Glycogenin is a self-glucosylating protein involved in the initiation reactions of glycogen biosynthesis. A gene on chromosome 3 encodes the muscle glycogenin and this X-linked gene encodes the glycogenin mainly present in liver; both are involved in blood glucose homeostasis. This gene has a short version on chromosome Y, which is 3' truncated and can not make a functional protein. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant X-2843032-C-G is Benign according to our data. Variant chrX-2843032-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317722.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.608 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GYG2NM_001079855.2 linkc.8-181C>G intron_variant Intron 2 of 10 ENST00000398806.8 NP_001073324.1 O15488-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GYG2ENST00000398806.8 linkc.8-181C>G intron_variant Intron 2 of 10 1 NM_001079855.2 ENSP00000381786.3 O15488-2

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
16
AN:
110614
Hom.:
0
Cov.:
22
AF XY:
0.000122
AC XY:
4
AN XY:
32914
show subpopulations
Gnomad AFR
AF:
0.0000988
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000193
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000208
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000827
AC:
8
AN:
96793
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
29537
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000108
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000157
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
15
AN:
392098
Hom.:
0
Cov.:
4
AF XY:
0.0000217
AC XY:
3
AN XY:
138096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000381
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000616
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000145
AC:
16
AN:
110614
Hom.:
0
Cov.:
22
AF XY:
0.000122
AC XY:
4
AN XY:
32914
show subpopulations
Gnomad4 AFR
AF:
0.0000988
Gnomad4 AMR
AF:
0.000193
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000208
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 16, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

GYG2-related disorder Benign:1
Apr 03, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.1
DANN
Benign
0.52

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: rs765257386; hg19: chrX-2761073; API