Genetic Variant GIGYF2:c.268-15_268-6delTTTTTTTTTT (chr2-232756197-CTTTTTTTTTT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001103146.3(GIGYF2):c.268-15_268-6delTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00575 in 710,618 control chromosomes in the GnomAD database, including 29 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 0)

Exomes 𝑓: 0.0062 ( 26 hom. )

Consequence

GIGYF2
NM_001103146.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

0 publications found

Variant links:

Genes affected

GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

GIGYF2 Gene-Disease associations (from GenCC):

Parkinson disease 11, autosomal dominant, susceptibility to
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

GIGYF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 347 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.268-15_268-6delTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 28	ENST00000373563.9	NP_001096616.1	Q6Y7W6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9 link	c.268-25_268-16delTTTTTTTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

347

AN:

102708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00149

Gnomad ASJ

AF:

0.000358

Gnomad EAS

AF:

0.000266

Gnomad SAS

AF:

0.00171

Gnomad FIN

AF:

0.00136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00491

Gnomad OTH

AF:

0.00228

GnomAD4 exome

AF:

0.00615

AC:

3739

AN:

607944

Hom.:

AF XY:

0.00567

AC XY:

1827

AN XY:

322386

show subpopulations

African (AFR)

AF:

0.00256

AC:

AN:

14868

American (AMR)

AF:

0.00155

AC:

AN:

25778

Ashkenazi Jewish (ASJ)

AF:

0.000311

AC:

AN:

16078

East Asian (EAS)

AF:

0.0000318

AC:

AN:

31438

South Asian (SAS)

AF:

0.00219

AC:

106

AN:

48302

European-Finnish (FIN)

AF:

0.000838

AC:

AN:

37014

Middle Eastern (MID)

AF:

0.00220

AC:

AN:

2268

European-Non Finnish (NFE)

AF:

0.00842

AC:

3390

AN:

402460

Other (OTH)

AF:

0.00414

AC:

123

AN:

29738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.628

Heterozygous variant carriers

122

245

367

490

612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00338

AC:

347

AN:

102674

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

146

AN XY:

47572

show subpopulations

African (AFR)

AF:

0.00234

AC:

AN:

26036

American (AMR)

AF:

0.00149

AC:

AN:

8742

Ashkenazi Jewish (ASJ)

AF:

0.000358

AC:

AN:

2792

East Asian (EAS)

AF:

0.000267

AC:

AN:

3746

South Asian (SAS)

AF:

0.00173

AC:

AN:

2896

European-Finnish (FIN)

AF:

0.00136

AC:

AN:

3676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.00491

AC:

258

AN:

52572

Other (OTH)

AF:

0.00226

AC:

AN:

1330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00117

Hom.:

144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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2-232756197-CTTTTTTTTTTTTTT-CTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over