dbSNP rs765257386: GYG2:p.Leu14Leu (chrX-2843032-C-G) – 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_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

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.608

Publications

0 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:

Genome browser will be placed here

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=-0.87).

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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003918.3. 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.8-181C>G		intron	N/A	NP_001073324.1	O15488-2
GYG2	NM_003918.3		c.42C>G	p.Leu14Leu	synonymous	Exon 3 of 12	NP_003909.2	O15488-1
GYG2	NM_001184703.2		c.42C>G	p.Leu14Leu	synonymous	Exon 3 of 10	NP_001171632.1	O15488-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG2	ENST00000381163.7	TSL:1	c.42C>G	p.Leu14Leu	synonymous	Exon 3 of 12	ENSP00000370555.3	O15488-1
GYG2	ENST00000398806.8	TSL:1 MANE Select	c.8-181C>G		intron	N/A	ENSP00000381786.3	O15488-2
GYG2	ENST00000958345.1		c.42C>G	p.Leu14Leu	synonymous	Exon 3 of 12	ENSP00000628404.1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

110614

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000827

AC:

AN:

96793

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

392098

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

138096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12249

American (AMR)

AF:

0.0000381

AC:

AN:

26256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14014

East Asian (EAS)

AF:

0.00

AC:

AN:

23259

South Asian (SAS)

AF:

0.00

AC:

AN:

36030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2323

European-Non Finnish (NFE)

AF:

0.0000616

AC:

AN:

227226

Other (OTH)

AF:

0.00

AC:

AN:

22413

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

110614

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

32914

show subpopulations

African (AFR)

AF:

0.0000988

AC:

AN:

30354

American (AMR)

AF:

0.000193

AC:

AN:

10374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2631

East Asian (EAS)

AF:

0.00

AC:

AN:

3516

South Asian (SAS)

AF:

0.00

AC:

AN:

2607

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5889

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000208

AC:

AN:

52834

Other (OTH)

AF:

0.00

AC:

AN:

1493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

GYG2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.52

PhyloP100

-0.61

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over