Genetic Variant GIGYF2:c.268-12_268-6delTTTTTTT (chr2-232756197-CTTTTTTT-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.268-12_268-6delTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 710,136 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 0 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 78 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.268-12_268-6delTTTTTTT		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_268-19delTTTTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.000759

AC:

AN:

102714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000797

Gnomad SAS

AF:

0.00240

Gnomad FIN

AF:

0.000272

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000475

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00106

AC:

645

AN:

607456

Hom.:

AF XY:

0.00115

AC XY:

370

AN XY:

322126

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

14858

American (AMR)

AF:

0.000816

AC:

AN:

25744

Ashkenazi Jewish (ASJ)

AF:

0.0000623

AC:

AN:

16064

East Asian (EAS)

AF:

0.00335

AC:

105

AN:

31384

South Asian (SAS)

AF:

0.00394

AC:

190

AN:

48270

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

36980

Middle Eastern (MID)

AF:

0.00132

AC:

AN:

2268

European-Non Finnish (NFE)

AF:

0.000619

AC:

249

AN:

402190

Other (OTH)

AF:

0.00128

AC:

AN:

29698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000760

AC:

AN:

102680

Hom.:

Cov.:

AF XY:

0.000988

AC XY:

AN XY:

47572

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

26042

American (AMR)

AF:

0.000686

AC:

AN:

8742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2792

East Asian (EAS)

AF:

0.000801

AC:

AN:

3746

South Asian (SAS)

AF:

0.00242

AC:

AN:

2896

European-Finnish (FIN)

AF:

0.000272

AC:

AN:

3676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.000476

AC:

AN:

52572

Other (OTH)

AF:

0.00

AC:

AN:

1330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

144

Bravo

AF:

0.000529

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-CTTTTTTT

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