NM_001103146.3:c.268-15_268-6delTTTTTTTTTT

Variant names:

• chr2-232756197-CTTTTTTTTTT-C
• rs759525243
• NM_001103146.3:c.268-15_268-6delTTTTTTTTTT

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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0062 (26 hom.)
• Consequence: GIGYF2 NM_001103146.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

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: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BS2: High AC in GnomAd4 at 347 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001103146.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	NM_001103146.3	MANE Select	c.268-15_268-6delTTTTTTTTTT		splice_region intron	N/A	NP_001096616.1	Q6Y7W6-1
	GIGYF2	NM_001103147.2		c.268-15_268-6delTTTTTTTTTT		splice_region intron	N/A	NP_001096617.1	Q6Y7W6-3
	GIGYF2	NM_015575.4		c.268-15_268-6delTTTTTTTTTT		splice_region intron	N/A	NP_056390.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	ENST00000373563.9	TSL:1 MANE Select	c.268-25_268-16delTTTTTTTTTT		intron	N/A	ENSP00000362664.5	Q6Y7W6-1
	GIGYF2	ENST00000409451.7	TSL:1	c.268-25_268-16delTTTTTTTTTT		intron	N/A	ENSP00000387170.3	Q6Y7W6-3
	GIGYF2	ENST00000409547.5	TSL:1	c.268-25_268-16delTTTTTTTTTT		intron	N/A	ENSP00000386537.1	Q6Y7W6-1

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 347 AN: 102708 Hom.: 3 Cov.: 0

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.: 26 AF XY: 0.00567 AC XY: 1827 AN XY: 322386

African (AFR) AF: 0.00256 AC: 38 AN: 14868

American (AMR) AF: 0.00155 AC: 40 AN: 25778

Ashkenazi Jewish (ASJ) AF: 0.000311 AC: 5 AN: 16078

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31438

South Asian (SAS) AF: 0.00219 AC: 106 AN: 48302

European-Finnish (FIN) AF: 0.000838 AC: 31 AN: 37014

Middle Eastern (MID) AF: 0.00220 AC: 5 AN: 2268

European-Non Finnish (NFE) AF: 0.00842 AC: 3390 AN: 402460

Other (OTH) AF: 0.00414 AC: 123 AN: 29738

GnomAD4 genome AF: 0.00338 AC: 347 AN: 102674 Hom.: 3 Cov.: 0 AF XY: 0.00307 AC XY: 146 AN XY: 47572

African (AFR) AF: 0.00234 AC: 61 AN: 26036

American (AMR) AF: 0.00149 AC: 13 AN: 8742

Ashkenazi Jewish (ASJ) AF: 0.000358 AC: 1 AN: 2792

East Asian (EAS) AF: 0.000267 AC: 1 AN: 3746

South Asian (SAS) AF: 0.00173 AC: 5 AN: 2896

European-Finnish (FIN) AF: 0.00136 AC: 5 AN: 3676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.00491 AC: 258 AN: 52572

Other (OTH) AF: 0.00226 AC: 3 AN: 1330

Alfa AF: 0.00117 Hom.: 144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs759525243; hg19: chr2-233620907;