Genetic Variant GYG2:c.8-278T>G (chrX-2842935-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001079855.2(GYG2):c.8-278T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 334,107 control chromosomes in the GnomAD database, including 14,037 homozygotes. There are 36,038 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 4417 hom., 9421 hem., cov: 20)

Exomes 𝑓: 0.35 ( 9620 hom. 26617 hem. )

Consequence

GYG2
NM_001079855.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.554

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-2842935-T-G is Benign according to our data. Variant chrX-2842935-T-G is described in ClinVar as Benign. ClinVar VariationId is 1234757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
GYG2	NM_001079855.2	MANE Select	c.8-278T>G	intron	N/A	NP_001073324.1	O15488-2
GYG2	NM_003918.3		c.8-63T>G	intron	N/A	NP_003909.2	O15488-1
GYG2	NM_001184702.2		c.8-278T>G	intron	N/A	NP_001171631.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GYG2	ENST00000398806.8	TSL:1 MANE Select	c.8-278T>G	intron	N/A	ENSP00000381786.3	O15488-2
GYG2	ENST00000381163.7	TSL:1	c.8-63T>G	intron	N/A	ENSP00000370555.3	O15488-1
GYG2	ENST00000958345.1		c.8-63T>G	intron	N/A	ENSP00000628404.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

35380

AN:

106462

Hom.:

4424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.410

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.322

GnomAD4 exome

AF:

0.354

AC:

80665

AN:

227598

Hom.:

9620

AF XY:

0.372

AC XY:

26617

AN XY:

71590

show subpopulations

African (AFR)

AF:

0.333

AC:

2541

AN:

7627

American (AMR)

AF:

0.317

AC:

5091

AN:

16067

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

2277

AN:

6710

East Asian (EAS)

AF:

0.414

AC:

5001

AN:

12069

South Asian (SAS)

AF:

0.425

AC:

11878

AN:

27964

European-Finnish (FIN)

AF:

0.294

AC:

3550

AN:

12078

Middle Eastern (MID)

AF:

0.374

AC:

315

AN:

842

European-Non Finnish (NFE)

AF:

0.346

AC:

45564

AN:

131573

Other (OTH)

AF:

0.351

AC:

4448

AN:

12668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1924

3848

5772

7696

9620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.332

AC:

35381

AN:

106509

Hom.:

4417

Cov.:

AF XY:

0.322

AC XY:

9421

AN XY:

29291

show subpopulations

African (AFR)

AF:

0.324

AC:

9463

AN:

29207

American (AMR)

AF:

0.297

AC:

2911

AN:

9797

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

898

AN:

2585

East Asian (EAS)

AF:

0.432

AC:

1430

AN:

3312

South Asian (SAS)

AF:

0.439

AC:

997

AN:

2272

European-Finnish (FIN)

AF:

0.246

AC:

1313

AN:

5348

Middle Eastern (MID)

AF:

0.405

AC:

AN:

205

European-Non Finnish (NFE)

AF:

0.339

AC:

17546

AN:

51692

Other (OTH)

AF:

0.325

AC:

466

AN:

1434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

863

1726

2590

3453

4316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.328

Hom.:

2129

Bravo

AF:

0.340

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.1

(source)

DANN

Benign

0.91

PhyloP100

-0.55

PromoterAI

-0.0021

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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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