Genetic Variant GYG2:c.-49C>T (chrX-2830140-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001079855.2(GYG2):c.-49C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,188,678 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 232 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 0.00050 ( 0 hom., 14 hem., cov: 24)

Exomes 𝑓: 0.00069 ( 0 hom. 218 hem. )

Consequence

GYG2
NM_001079855.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.964

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]

GYG2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-2830140-C-T is Benign according to our data. Variant chrX-2830140-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 516935.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYG2	NM_001079855.2 link	c.-49C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	ENST00000398806.8	NP_001073324.1	O15488-2
GYG2	NM_001079855.2 link	c.-49C>T		5_prime_UTR_variant	Exon 2 of 11	ENST00000398806.8	NP_001073324.1	O15488-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYG2	ENST00000398806 link	c.-49C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	1	NM_001079855.2	ENSP00000381786.3		O15488-2
GYG2	ENST00000398806 link	c.-49C>T		5_prime_UTR_variant	Exon 2 of 11	1	NM_001079855.2	ENSP00000381786.3		O15488-2

Frequencies

GnomAD3 genomes

AF:

0.000497

AC:

AN:

112709

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

AN XY:

34883

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000186

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:

0.000883

Gnomad OTH

AF:

0.000662

GnomAD3 exomes

AF:

0.000324

AC:

AN:

175926

Hom.:

AF XY:

0.000241

AC XY:

AN XY:

62348

show subpopulations

Gnomad AFR exome

AF:

0.0000785

Gnomad AMR exome

AF:

0.0000373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000694

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000693

AC:

746

AN:

1075969

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

218

AN XY:

345247

show subpopulations

Gnomad4 AFR exome

AF:

0.000192

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.0000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000862

Gnomad4 OTH exome

AF:

0.000640

GnomAD4 genome

AF:

0.000497

AC:

AN:

112709

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

AN XY:

34883

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000186

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000883

Gnomad4 OTH

AF:

0.000662

Alfa

AF:

0.000781

Hom.:

Bravo

AF:

0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 12, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.8

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over