ENST00000381163.7:c.77C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000381163.7(GYG2):c.77C>A(p.Ala26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 541,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 53 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00019 ( 0 hom. 49 hem. )

Consequence

GYG2
ENST00000381163.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.116

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011960328).

BP6

Variant X-2843067-C-A is Benign according to our data. Variant chrX-2843067-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1317898.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381163.7. 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.8-146C>A		intron	N/A	NP_001073324.1	O15488-2
GYG2	NM_003918.3		c.77C>A	p.Ala26Asp	missense	Exon 3 of 12	NP_003909.2	O15488-1
GYG2	NM_001184703.2		c.77C>A	p.Ala26Asp	missense	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.77C>A	p.Ala26Asp	missense	Exon 3 of 12	ENSP00000370555.3	O15488-1
GYG2	ENST00000398806.8	TSL:1 MANE Select	c.8-146C>A		intron	N/A	ENSP00000381786.3	O15488-2
GYG2	ENST00000958345.1		c.77C>A	p.Ala26Asp	missense	Exon 3 of 12	ENSP00000628404.1

Frequencies

GnomAD3 genomes

AF:

0.0000894

AC:

AN:

111824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00149

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000213

AC:

AN:

112653

AF XY:

0.000434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

AN:

429860

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

151448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13182

American (AMR)

AF:

0.00

AC:

AN:

27233

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14729

East Asian (EAS)

AF:

0.00

AC:

AN:

24336

South Asian (SAS)

AF:

0.00159

AC:

AN:

37674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34087

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2844

European-Non Finnish (NFE)

AF:

0.0000675

AC:

AN:

251960

Other (OTH)

AF:

0.000126

AC:

AN:

23815

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000894

AC:

AN:

111874

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34074

show subpopulations

African (AFR)

AF:

0.0000973

AC:

AN:

30845

American (AMR)

AF:

0.00

AC:

AN:

10554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00149

AC:

AN:

2678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53122

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.0000712

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000166

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.6

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0026

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.60

M_CAP

Benign

0.0017

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

-0.12

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.57

REVEL

Benign

0.036

Sift

Uncertain

0.025

Sift4G

Benign

0.27

Polyphen

0.91

Vest4

0.13

MutPred

0.23

Gain of relative solvent accessibility (P = 0.09)

MVP

0.28

MPC

0.20

ClinPred

0.080

GERP RS

0.50

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.41

gMVP

0.33

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