Genetic Variant GYG2:p.Leu11Leu (chrX-2843236-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001079855.2(GYG2):c.31C>T(p.Leu11Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,203,329 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000027 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

GYG2
NM_001079855.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.799

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-2843236-C-T is Benign according to our data. Variant chrX-2843236-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 391216.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.799 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079855.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG2	NM_001079855.2	MANE Select	c.31C>T	p.Leu11Leu	synonymous	Exon 3 of 11	NP_001073324.1	O15488-2
GYG2	NM_003918.3		c.124C>T	p.Leu42Leu	synonymous	Exon 4 of 12	NP_003909.2	O15488-1
GYG2	NM_001184702.2		c.31C>T	p.Leu11Leu	synonymous	Exon 3 of 11	NP_001171631.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG2	ENST00000398806.8	TSL:1 MANE Select	c.31C>T	p.Leu11Leu	synonymous	Exon 3 of 11	ENSP00000381786.3	O15488-2
GYG2	ENST00000381163.7	TSL:1	c.124C>T	p.Leu42Leu	synonymous	Exon 4 of 12	ENSP00000370555.3	O15488-1
GYG2	ENST00000958345.1		c.124C>T	p.Leu42Leu	synonymous	Exon 4 of 12	ENSP00000628404.1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000977

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.16e-7

AC:

AN:

1091649

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357321

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26287

American (AMR)

AF:

0.00

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19341

East Asian (EAS)

AF:

0.00

AC:

AN:

30147

South Asian (SAS)

AF:

0.00

AC:

AN:

53928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

836262

Other (OTH)

AF:

0.00

AC:

AN:

45865

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111680

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33836

show subpopulations

African (AFR)

AF:

0.0000977

AC:

AN:

30719

American (AMR)

AF:

0.00

AC:

AN:

10492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3535

South Asian (SAS)

AF:

0.00

AC:

AN:

2658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53102

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.0

(source)

DANN

Benign

0.66

PhyloP100

0.80

PromoterAI

-0.0026

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over