Genetic Variant GIGYF2:c.268-13_268-6delTTTTTTTT (chr2-232756197-CTTTTTTTT-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.268-13_268-6delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 710,506 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 0.00013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00015 ( 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 13 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.268-13_268-6delTTTTTTTT		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_268-18delTTTTTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.000127

AC:

AN:

102708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000571

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000148

AC:

AN:

607832

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

322328

show subpopulations

African (AFR)

AF:

0.000404

AC:

AN:

14864

American (AMR)

AF:

0.000155

AC:

AN:

25770

Ashkenazi Jewish (ASJ)

AF:

0.000124

AC:

AN:

16078

East Asian (EAS)

AF:

0.000191

AC:

AN:

31422

South Asian (SAS)

AF:

0.000104

AC:

AN:

48290

European-Finnish (FIN)

AF:

0.0000270

AC:

AN:

37010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2268

European-Non Finnish (NFE)

AF:

0.000157

AC:

AN:

402398

Other (OTH)

AF:

0.000101

AC:

AN:

29732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000127

AC:

AN:

102674

Hom.:

Cov.:

AF XY:

0.0000841

AC XY:

AN XY:

47570

show subpopulations

African (AFR)

AF:

0.000384

AC:

AN:

26038

American (AMR)

AF:

0.00

AC:

AN:

8742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2792

East Asian (EAS)

AF:

0.00

AC:

AN:

3746

South Asian (SAS)

AF:

0.00

AC:

AN:

2896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.0000571

AC:

AN:

52570

Other (OTH)

AF:

0.00

AC:

AN:

1330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

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:

0.000128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Splicing

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

Publications

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2-232756197-CTTTTTTTTTTTTTT-CTTTTTT

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