2-232756197-CTTTTTTTTTTTTTT-CTTTTTT

Variant names:

• chr2-232756197-CTTTTTTTT-C
• rs759525243
• NM_001103146.3:c.268-13_268-6delTTTTTTTT

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
• 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 13 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.268-13_268-6delTTTTTTTT		splice_region intron	N/A	NP_001096616.1	Q6Y7W6-1
	GIGYF2	NM_001103147.2		c.268-13_268-6delTTTTTTTT		splice_region intron	N/A	NP_001096617.1	Q6Y7W6-3
	GIGYF2	NM_015575.4		c.268-13_268-6delTTTTTTTT		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_268-18delTTTTTTTT		intron	N/A	ENSP00000362664.5	Q6Y7W6-1
	GIGYF2	ENST00000409451.7	TSL:1	c.268-25_268-18delTTTTTTTT		intron	N/A	ENSP00000387170.3	Q6Y7W6-3
	GIGYF2	ENST00000409547.5	TSL:1	c.268-25_268-18delTTTTTTTT		intron	N/A	ENSP00000386537.1	Q6Y7W6-1

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 13 AN: 102708 Hom.: 0 Cov.: 0

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: 90 AN: 607832 Hom.: 0 AF XY: 0.000121 AC XY: 39 AN XY: 322328

African (AFR) AF: 0.000404 AC: 6 AN: 14864

American (AMR) AF: 0.000155 AC: 4 AN: 25770

Ashkenazi Jewish (ASJ) AF: 0.000124 AC: 2 AN: 16078

East Asian (EAS) AF: 0.000191 AC: 6 AN: 31422

South Asian (SAS) AF: 0.000104 AC: 5 AN: 48290

European-Finnish (FIN) AF: 0.0000270 AC: 1 AN: 37010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2268

European-Non Finnish (NFE) AF: 0.000157 AC: 63 AN: 402398

Other (OTH) AF: 0.000101 AC: 3 AN: 29732

GnomAD4 genome AF: 0.000127 AC: 13 AN: 102674 Hom.: 0 Cov.: 0 AF XY: 0.0000841 AC XY: 4 AN XY: 47570

African (AFR) AF: 0.000384 AC: 10 AN: 26038

American (AMR) AF: 0.00 AC: 0 AN: 8742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2792

East Asian (EAS) AF: 0.00 AC: 0 AN: 3746

South Asian (SAS) AF: 0.00 AC: 0 AN: 2896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3676

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

European-Non Finnish (NFE) AF: 0.0000571 AC: 3 AN: 52570

Other (OTH) AF: 0.00 AC: 0 AN: 1330

Alfa AF: 0.00 Hom.: 144

Bravo AF: 0.000128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

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;